CN1515259A - 用作cetp抑制剂的4-氨基取代的-2-取代的-1，2，3，4-四氢喹啉 - Google Patents
用作cetp抑制剂的4-氨基取代的-2-取代的-1，2，3，4-四氢喹啉 Download PDFInfo
- Publication number
- CN1515259A CN1515259A CNA2004100049599A CN200410004959A CN1515259A CN 1515259 A CN1515259 A CN 1515259A CN A2004100049599 A CNA2004100049599 A CN A2004100049599A CN 200410004959 A CN200410004959 A CN 200410004959A CN 1515259 A CN1515259 A CN 1515259A
- Authority
- CN
- China
- Prior art keywords
- chemical compound
- chosen wantonly
- alkyl
- replace
- replacements
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 title abstract description 9
- -1 4-aminosubstituted-2-substituted-1,2,3,4-tetrahydroquinoline Chemical class 0.000 title description 210
- 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 395
- 239000000651 prodrug Substances 0.000 claims abstract description 128
- 229940002612 prodrug Drugs 0.000 claims abstract description 128
- 150000003839 salts Chemical class 0.000 claims abstract description 90
- 241000124008 Mammalia Species 0.000 claims abstract description 56
- 239000003112 inhibitor Substances 0.000 claims abstract description 46
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 197
- 229910052757 nitrogen Inorganic materials 0.000 claims description 137
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 106
- 229910052799 carbon Inorganic materials 0.000 claims description 93
- 238000011282 treatment Methods 0.000 claims description 93
- 125000004043 oxo group Chemical group O=* 0.000 claims description 91
- 229910052717 sulfur Inorganic materials 0.000 claims description 91
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 89
- 239000011593 sulfur Substances 0.000 claims description 89
- 229910052760 oxygen Inorganic materials 0.000 claims description 86
- 239000001301 oxygen Substances 0.000 claims description 84
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 76
- 229910052736 halogen Inorganic materials 0.000 claims description 75
- 150000002367 halogens Chemical class 0.000 claims description 72
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 68
- 125000003545 alkoxy group Chemical group 0.000 claims description 68
- 239000000203 mixture Substances 0.000 claims description 68
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 67
- 125000005842 heteroatom Chemical group 0.000 claims description 63
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 60
- 229910052731 fluorine Inorganic materials 0.000 claims description 60
- 239000011737 fluorine Substances 0.000 claims description 60
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 56
- 229920006395 saturated elastomer Polymers 0.000 claims description 56
- 238000010572 single replacement reaction Methods 0.000 claims description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 43
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 43
- 125000001424 substituent group Chemical group 0.000 claims description 35
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 34
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 33
- 125000004414 alkyl thio group Chemical group 0.000 claims description 32
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 31
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 24
- 150000001721 carbon Chemical group 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 21
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 20
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 20
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 20
- 230000028327 secretion Effects 0.000 claims description 19
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 16
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 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 9
- 239000003613 bile acid Substances 0.000 claims description 9
- 239000002552 dosage form Substances 0.000 claims description 9
- 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 claims description 8
- 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 claims description 8
- 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 claims description 8
- 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 claims description 8
- 239000003963 antioxidant agent Substances 0.000 claims description 8
- 230000003078 antioxidant effect Effects 0.000 claims description 8
- 229940125753 fibrate Drugs 0.000 claims description 8
- 229960003765 fluvastatin Drugs 0.000 claims description 8
- 229960004844 lovastatin Drugs 0.000 claims description 8
- 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 claims description 8
- 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 claims description 8
- 229960003512 nicotinic acid Drugs 0.000 claims description 8
- 239000011664 nicotinic acid Substances 0.000 claims description 8
- 235000001968 nicotinic acid Nutrition 0.000 claims description 8
- 229960002965 pravastatin Drugs 0.000 claims description 8
- 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 claims description 8
- 229960002855 simvastatin Drugs 0.000 claims description 8
- 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 claims description 8
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 7
- IZVFFXVYBHFIHY-SKCNUYALSA-N 5alpha-cholest-7-en-3beta-ol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@H](C)CCCC(C)C)CC[C@H]33)C)C3=CC[C@H]21 IZVFFXVYBHFIHY-SKCNUYALSA-N 0.000 claims description 7
- 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 claims description 7
- 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 claims description 7
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims description 7
- 230000003143 atherosclerotic effect Effects 0.000 claims description 7
- 229960005370 atorvastatin Drugs 0.000 claims description 7
- 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 claims description 7
- 239000002738 chelating agent Substances 0.000 claims description 7
- 239000003456 ion exchange resin Substances 0.000 claims description 7
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 7
- 239000012622 synthetic inhibitor Substances 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 7
- 125000001118 alkylidene group Chemical group 0.000 claims description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
- 229910052727 yttrium Inorganic materials 0.000 claims description 4
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 3
- 239000000890 drug combination Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 2
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 2
- 239000012190 activator Substances 0.000 claims description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000008024 pharmaceutical diluent Substances 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 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 abstract description 48
- 108010010234 HDL Lipoproteins Proteins 0.000 abstract description 41
- 102000015779 HDL Lipoproteins Human genes 0.000 abstract description 41
- 201000001320 Atherosclerosis Diseases 0.000 abstract description 18
- 235000012000 cholesterol Nutrition 0.000 abstract description 18
- 201000010099 disease Diseases 0.000 abstract description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 16
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 15
- 150000002632 lipids Chemical class 0.000 abstract description 15
- 238000008214 LDL Cholesterol Methods 0.000 abstract description 13
- 108010023302 HDL Cholesterol Proteins 0.000 abstract description 8
- 108010028554 LDL Cholesterol Proteins 0.000 abstract description 7
- 150000003626 triacylglycerols Chemical class 0.000 abstract 2
- 238000000034 method Methods 0.000 description 109
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 77
- 238000005160 1H NMR spectroscopy Methods 0.000 description 68
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 58
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
- 239000002585 base Substances 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 150000001412 amines Chemical class 0.000 description 47
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 46
- 239000000243 solution Substances 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 38
- 125000006239 protecting group Chemical group 0.000 description 31
- 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 description 30
- 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 210000002381 plasma Anatomy 0.000 description 29
- 239000002253 acid Substances 0.000 description 27
- 238000002360 preparation method Methods 0.000 description 27
- 238000011287 therapeutic dose Methods 0.000 description 27
- 239000002798 polar solvent Substances 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 238000005481 NMR spectroscopy Methods 0.000 description 24
- 230000000694 effects Effects 0.000 description 24
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 22
- 239000002904 solvent Substances 0.000 description 21
- 239000003826 tablet Substances 0.000 description 21
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 18
- 239000003513 alkali Substances 0.000 description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 17
- 150000001408 amides Chemical class 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 description 14
- 239000002775 capsule Substances 0.000 description 14
- 150000002148 esters Chemical class 0.000 description 14
- 108010038232 microsomal triglyceride transfer protein Proteins 0.000 description 14
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 14
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 13
- 208000028867 ischemia Diseases 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 208000032928 Dyslipidaemia Diseases 0.000 description 12
- 108010007622 LDL Lipoproteins Proteins 0.000 description 12
- 102000007330 LDL Lipoproteins Human genes 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 12
- 208000017170 Lipid metabolism disease Diseases 0.000 description 11
- 102000004895 Lipoproteins Human genes 0.000 description 11
- 108090001030 Lipoproteins Proteins 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 238000010511 deprotection reaction Methods 0.000 description 11
- 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 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 241000283973 Oryctolagus cuniculus Species 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 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 10
- 230000008859 change Effects 0.000 description 10
- 206010012601 diabetes mellitus Diseases 0.000 description 10
- 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 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 238000012545 processing Methods 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 229940031439 squalene Drugs 0.000 description 10
- 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 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 208000008589 Obesity Diseases 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000003213 activating effect Effects 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 239000002158 endotoxin Substances 0.000 description 9
- 235000020824 obesity Nutrition 0.000 description 9
- 239000000376 reactant Substances 0.000 description 9
- 230000002792 vascular Effects 0.000 description 9
- 206010008190 Cerebrovascular accident Diseases 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 208000035150 Hypercholesterolemia Diseases 0.000 description 8
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 8
- 206010020772 Hypertension Diseases 0.000 description 8
- 206010021024 Hypolipidaemia Diseases 0.000 description 8
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 8
- 206010063837 Reperfusion injury Diseases 0.000 description 8
- 229940119502 Squalene cyclase inhibitor Drugs 0.000 description 8
- 229940123185 Squalene epoxidase inhibitor Drugs 0.000 description 8
- 208000006011 Stroke Diseases 0.000 description 8
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 8
- 238000002399 angioplasty Methods 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 230000003197 catalytic effect Effects 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 208000029078 coronary artery disease Diseases 0.000 description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 8
- 201000001386 familial hypercholesterolemia Diseases 0.000 description 8
- 208000029498 hypoalphalipoproteinemia Diseases 0.000 description 8
- 208000010125 myocardial infarction Diseases 0.000 description 8
- 208000037803 restenosis Diseases 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 238000012546 transfer Methods 0.000 description 8
- 208000037487 Endotoxemia Diseases 0.000 description 7
- 208000018262 Peripheral vascular disease Diseases 0.000 description 7
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 125000000524 functional group Chemical group 0.000 description 7
- 208000006575 hypertriglyceridemia Diseases 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 150000002923 oximes Chemical class 0.000 description 7
- 235000011121 sodium hydroxide Nutrition 0.000 description 7
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 6
- IXAFDJANUSIELV-UHFFFAOYSA-N C(=O)OC(C)C.CC1NC2=CC=CC=C2CC1 Chemical compound C(=O)OC(C)C.CC1NC2=CC=CC=C2CC1 IXAFDJANUSIELV-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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
- 150000001350 alkyl halides Chemical class 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 6
- 230000002354 daily effect Effects 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 229920006008 lipopolysaccharide Polymers 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 6
- 238000007911 parenteral administration Methods 0.000 description 6
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 206010002383 Angina Pectoris Diseases 0.000 description 5
- CUFADOHDVXYNJB-UHFFFAOYSA-N C(=O)OC(C)C.N1CCCC2=CC=CC=C12.CF Chemical compound C(=O)OC(C)C.N1CCCC2=CC=CC=C12.CF CUFADOHDVXYNJB-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 208000035126 Facies Diseases 0.000 description 5
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 241000699660 Mus musculus Species 0.000 description 5
- 206010040070 Septic Shock Diseases 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 102000005782 Squalene Monooxygenase Human genes 0.000 description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
- 230000036983 biotransformation Effects 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 238000002372 labelling Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 125000002971 oxazolyl group Chemical group 0.000 description 5
- 239000003880 polar aprotic solvent Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 230000036303 septic shock Effects 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000011830 transgenic mouse model Methods 0.000 description 5
- AOHWLRLIIDCTEX-UHFFFAOYSA-N C(=O)OCC.CC1NC2=CC=CC=C2CC1 Chemical compound C(=O)OCC.CC1NC2=CC=CC=C2CC1 AOHWLRLIIDCTEX-UHFFFAOYSA-N 0.000 description 4
- SXWZUSQAOSYOGI-UHFFFAOYSA-N C(=O)OCC.N1CCCC2=CC=CC=C12.CF Chemical compound C(=O)OCC.N1CCCC2=CC=CC=C12.CF SXWZUSQAOSYOGI-UHFFFAOYSA-N 0.000 description 4
- IACSIWNHQUDEJH-UHFFFAOYSA-N C(=O)OCCC.CC1NC2=CC=CC=C2CC1 Chemical compound C(=O)OCCC.CC1NC2=CC=CC=C2CC1 IACSIWNHQUDEJH-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 108010000775 Hydroxymethylglutaryl-CoA synthase Proteins 0.000 description 4
- 102100028888 Hydroxymethylglutaryl-CoA synthase, cytoplasmic Human genes 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
- 241001597008 Nomeidae Species 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 208000002352 blister Diseases 0.000 description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 238000005755 formation reaction Methods 0.000 description 4
- 150000004678 hydrides Chemical class 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
- 150000002466 imines Chemical class 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000012856 packing Methods 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 4
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000001544 thienyl group Chemical group 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- BQPPJGMMIYJVBR-UHFFFAOYSA-N (10S)-3c-Acetoxy-4.4.10r.13c.14t-pentamethyl-17c-((R)-1.5-dimethyl-hexen-(4)-yl)-(5tH)-Delta8-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products CC12CCC(OC(C)=O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C BQPPJGMMIYJVBR-UHFFFAOYSA-N 0.000 description 3
- CHGIKSSZNBCNDW-UHFFFAOYSA-N (3beta,5alpha)-4,4-Dimethylcholesta-8,24-dien-3-ol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21 CHGIKSSZNBCNDW-UHFFFAOYSA-N 0.000 description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 3
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 3
- XYTLYKGXLMKYMV-UHFFFAOYSA-N 14alpha-methylzymosterol Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C XYTLYKGXLMKYMV-UHFFFAOYSA-N 0.000 description 3
- FPTJELQXIUUCEY-UHFFFAOYSA-N 3beta-Hydroxy-lanostan Natural products C1CC2C(C)(C)C(O)CCC2(C)C2C1C1(C)CCC(C(C)CCCC(C)C)C1(C)CC2 FPTJELQXIUUCEY-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- BKLIAINBCQPSOV-UHFFFAOYSA-N Gluanol Natural products CC(C)CC=CC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(O)C(C)(C)C4CC3 BKLIAINBCQPSOV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101000733802 Homo sapiens Apolipoprotein A-I Proteins 0.000 description 3
- LOPKHWOTGJIQLC-UHFFFAOYSA-N Lanosterol Natural products CC(CCC=C(C)C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 LOPKHWOTGJIQLC-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- CAHGCLMLTWQZNJ-UHFFFAOYSA-N Nerifoliol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C CAHGCLMLTWQZNJ-UHFFFAOYSA-N 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 150000004982 aromatic amines Chemical class 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 230000037058 blood plasma level Effects 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 235000013877 carbamide Nutrition 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- QBSJHOGDIUQWTH-UHFFFAOYSA-N dihydrolanosterol Natural products CC(C)CCCC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 QBSJHOGDIUQWTH-UHFFFAOYSA-N 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- CAHGCLMLTWQZNJ-RGEKOYMOSA-N lanosterol Chemical compound C([C@]12C)C[C@@H](O)C(C)(C)[C@H]1CCC1=C2CC[C@]2(C)[C@H]([C@H](CCC=C(C)C)C)CC[C@@]21C CAHGCLMLTWQZNJ-RGEKOYMOSA-N 0.000 description 3
- 229940058690 lanosterol Drugs 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000000630 rising effect Effects 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 3
- 239000001117 sulphuric acid Substances 0.000 description 3
- 235000011149 sulphuric acid Nutrition 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 3
- 125000000335 thiazolyl group Chemical group 0.000 description 3
- 150000003568 thioethers Chemical group 0.000 description 3
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 3
- 230000001131 transforming effect Effects 0.000 description 3
- 210000003462 vein Anatomy 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
- LOZWAPSEEHRYPG-UHFFFAOYSA-N 1,4-dithiane Chemical compound C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- ZDVRPKUWYQVVDX-UHFFFAOYSA-N 2-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC=C1C=O ZDVRPKUWYQVVDX-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- 108010059886 Apolipoprotein A-I Proteins 0.000 description 2
- 102000005666 Apolipoprotein A-I Human genes 0.000 description 2
- 101710095342 Apolipoprotein B Proteins 0.000 description 2
- 102100040202 Apolipoprotein B-100 Human genes 0.000 description 2
- 102000007592 Apolipoproteins Human genes 0.000 description 2
- 108010071619 Apolipoproteins Proteins 0.000 description 2
- 102000018616 Apolipoproteins B Human genes 0.000 description 2
- 108010027006 Apolipoproteins B Proteins 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 241000228212 Aspergillus Species 0.000 description 2
- FHWHVYIACLCLSP-UHFFFAOYSA-N C(=O)OC(C)(C)C.CC1NC2=CC=CC=C2CC1 Chemical compound C(=O)OC(C)(C)C.CC1NC2=CC=CC=C2CC1 FHWHVYIACLCLSP-UHFFFAOYSA-N 0.000 description 2
- BDZREXXLUNMGHT-UHFFFAOYSA-N C(=O)OCC.N1=CC=CC2=CC=CC=C12 Chemical compound C(=O)OCC.N1=CC=CC2=CC=CC=C12 BDZREXXLUNMGHT-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 241000588724 Escherichia coli Species 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 208000000501 Lipidoses Diseases 0.000 description 2
- 206010024585 Lipidosis Diseases 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
- 229910000545 Nickel–aluminium alloy Inorganic materials 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 241000534944 Thia Species 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 108010069201 VLDL Cholesterol Proteins 0.000 description 2
- NRAINUFKKPBZQY-UHFFFAOYSA-N [O]C1CC1 Chemical compound [O]C1CC1 NRAINUFKKPBZQY-UHFFFAOYSA-N 0.000 description 2
- 150000001263 acyl chlorides Chemical class 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000005236 alkanoylamino group Chemical group 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N boron trifluoride etherate Substances FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- FBHSPRKOSMHSIF-GRMWVWQJSA-N deflazacort Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)=N[C@@]3(C(=O)COC(=O)C)[C@@]1(C)C[C@@H]2O FBHSPRKOSMHSIF-GRMWVWQJSA-N 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000003810 ethyl acetate extraction Methods 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 235000015110 jellies Nutrition 0.000 description 2
- 239000008274 jelly Substances 0.000 description 2
- 150000002596 lactones Chemical class 0.000 description 2
- 210000000088 lip Anatomy 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- RNTRDTWDTOZSEV-UHFFFAOYSA-N norphytene Natural products CC(C)CCCC(C)CCCC(C)CCCC(C)=C RNTRDTWDTOZSEV-UHFFFAOYSA-N 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 150000002902 organometallic compounds Chemical class 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- QQVIHTHCMHWDBS-UHFFFAOYSA-N perisophthalic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 2
- 239000003444 phase transfer catalyst Substances 0.000 description 2
- JHYGKRLFANBDIF-UHFFFAOYSA-N phosphane;triphenylphosphane Chemical compound P.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 JHYGKRLFANBDIF-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- 229930185107 quinolinone Natural products 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 102000030633 squalene cyclase Human genes 0.000 description 2
- 108010088324 squalene cyclase Proteins 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 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
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- RRKODOZNUZCUBN-CCAGOZQPSA-N (1z,3z)-cycloocta-1,3-diene Chemical compound C1CC\C=C/C=C\C1 RRKODOZNUZCUBN-CCAGOZQPSA-N 0.000 description 1
- CCZIACKSUCMORE-SCYNACPDSA-N (2R,4S)-2-ethyl-6-(trifluoromethyl)-1,2,3,4-tetrahydroquinolin-4-amine propyl formate Chemical compound C(=O)OCCC.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)CC CCZIACKSUCMORE-SCYNACPDSA-N 0.000 description 1
- KZFBOLXTZBYPGP-CFILVAQYSA-N (2R,4S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-ethyl-6-(trifluoromethyl)-1,2,3,4-tetrahydroquinolin-4-amine propan-2-yl formate Chemical compound C(=O)OC(C)C.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)CC)C=C(C1)C(F)(F)F)(F)F KZFBOLXTZBYPGP-CFILVAQYSA-N 0.000 description 1
- UXNWTASNUNMNMV-CFILVAQYSA-N (2R,4S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-ethyl-6-(trifluoromethyl)-1,2,3,4-tetrahydroquinolin-4-amine propyl formate Chemical compound C(=O)OCCC.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)CC)C=C(C1)C(F)(F)F)(F)F UXNWTASNUNMNMV-CFILVAQYSA-N 0.000 description 1
- PHJNKHPDAVMQJD-CVJFODCESA-N (2R,4S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydroquinolin-4-amine ethyl formate Chemical compound C(=O)OCC.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)C)C=C(C1)C(F)(F)F)(F)F PHJNKHPDAVMQJD-CVJFODCESA-N 0.000 description 1
- AVYCMTMTHCQDKZ-CVJFODCESA-N (2R,4S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydroquinolin-4-amine propyl formate Chemical compound C(=O)OCCC.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)C)C=C(C1)C(F)(F)F)(F)F AVYCMTMTHCQDKZ-CVJFODCESA-N 0.000 description 1
- WMRQRFUEBVUOQZ-JGAZGGJJSA-N (2S,4S)-2-cyclopropyl-6-(trifluoromethyl)-1,2,3,4-tetrahydroquinolin-4-amine propan-2-yl formate Chemical compound C(=O)OC(C)C.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)C1CC1 WMRQRFUEBVUOQZ-JGAZGGJJSA-N 0.000 description 1
- MFYLRNKOXORIPK-UHFFFAOYSA-N (3-nitrophenyl)-phenylmethanone Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 MFYLRNKOXORIPK-UHFFFAOYSA-N 0.000 description 1
- ZYMCBJWUWHHVRX-UHFFFAOYSA-N (4-nitrophenyl)-phenylmethanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)C1=CC=CC=C1 ZYMCBJWUWHHVRX-UHFFFAOYSA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- VLSDXINSOMDCBK-BQYQJAHWSA-N (E)-1,1'-azobis(N,N-dimethylformamide) Chemical compound CN(C)C(=O)\N=N\C(=O)N(C)C VLSDXINSOMDCBK-BQYQJAHWSA-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
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- JZTKNVMVUVSGJF-UHFFFAOYSA-N 1,2,3,5-oxatriazole Chemical compound C=1N=NON=1 JZTKNVMVUVSGJF-UHFFFAOYSA-N 0.000 description 1
- 150000000177 1,2,3-triazoles Chemical class 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 1
- VCZQYTJRWNRPHF-UHFFFAOYSA-N 1,2-dioxin Chemical compound O1OC=CC=C1 VCZQYTJRWNRPHF-UHFFFAOYSA-N 0.000 description 1
- PCGDBWLKAYKBTN-UHFFFAOYSA-N 1,2-dithiole Chemical compound C1SSC=C1 PCGDBWLKAYKBTN-UHFFFAOYSA-N 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- LORRLQMLLQLPSJ-UHFFFAOYSA-N 1,3,5-trithiane Chemical compound C1SCSCS1 LORRLQMLLQLPSJ-UHFFFAOYSA-N 0.000 description 1
- IVJFXSLMUSQZMC-UHFFFAOYSA-N 1,3-dithiole Chemical compound C1SC=CS1 IVJFXSLMUSQZMC-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000005851 1-(N-(alkoxycarbonyl)amino)ethyl group Chemical group 0.000 description 1
- 125000005848 1-(alkoxycarbonyloxy)ethyl group Chemical group 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N 1-Heptene Chemical class CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- BCMYXYHEMGPZJN-UHFFFAOYSA-N 1-chloro-2-isocyanatoethane Chemical compound ClCCN=C=O BCMYXYHEMGPZJN-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- YVTPINJIEGFACL-UHFFFAOYSA-N 1-piperidin-1-yloxypiperidine Chemical compound C1CCCCN1ON1CCCCC1 YVTPINJIEGFACL-UHFFFAOYSA-N 0.000 description 1
- 125000005955 1H-indazolyl group Chemical group 0.000 description 1
- KRNSYSYRLQDHDK-UHFFFAOYSA-N 2,3-Cyclopentenopyridine Natural products C1=CN=C2CCCC2=C1 KRNSYSYRLQDHDK-UHFFFAOYSA-N 0.000 description 1
- DGNMALJXEGQNKL-UHFFFAOYSA-N 2-(1h-1,2,4-triazol-5-ylmethyl)-3,4-dihydro-1h-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC1=NC=NN1 DGNMALJXEGQNKL-UHFFFAOYSA-N 0.000 description 1
- PAWSKKHEEYTXSA-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 PAWSKKHEEYTXSA-UHFFFAOYSA-N 0.000 description 1
- MCSJGXLZPITMIH-UHFFFAOYSA-N 2-aminobutane-1,1,1-triol Chemical class CCC(N)C(O)(O)O MCSJGXLZPITMIH-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- ZPSJGADGUYYRKE-UHFFFAOYSA-N 2H-pyran-2-one Chemical compound O=C1C=CC=CO1 ZPSJGADGUYYRKE-UHFFFAOYSA-N 0.000 description 1
- HPYLZSUEFFQHRS-UHFFFAOYSA-N 2h-1,2,4-oxadiazine Chemical compound N1OC=CN=C1 HPYLZSUEFFQHRS-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
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- WXYDKGMJJFFORR-UHFFFAOYSA-N 3-methyl-1-(3-methylbutylsulfinyl)butane Chemical compound CC(C)CCS(=O)CCC(C)C WXYDKGMJJFFORR-UHFFFAOYSA-N 0.000 description 1
- 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- NBOCQTNZUPTTEI-UHFFFAOYSA-N 4-[4-(hydrazinesulfonyl)phenoxy]benzenesulfonohydrazide Chemical compound C1=CC(S(=O)(=O)NN)=CC=C1OC1=CC=C(S(=O)(=O)NN)C=C1 NBOCQTNZUPTTEI-UHFFFAOYSA-N 0.000 description 1
- 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
- UCZQXJKDCHCTAI-UHFFFAOYSA-N 4h-1,3-dioxine Chemical compound C1OCC=CO1 UCZQXJKDCHCTAI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- ZIUYHTQZEPDUCZ-UHFFFAOYSA-N 7h-pyrrolo[2,3-h]quinoline Chemical compound C1=CN=C2C(C=CN3)=C3C=CC2=C1 ZIUYHTQZEPDUCZ-UHFFFAOYSA-N 0.000 description 1
- JGLHXBNHKQAROV-UHFFFAOYSA-N 9-methoxy-9h-fluorene Chemical compound C1=CC=C2C(OC)C3=CC=CC=C3C2=C1 JGLHXBNHKQAROV-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 102000006410 Apoproteins Human genes 0.000 description 1
- 108010083590 Apoproteins Proteins 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 239000007848 Bronsted acid Substances 0.000 description 1
- XCFFKUNKGYHDDH-CVJFODCESA-N C(=O)OC(C)C.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)C)C=C(C1)C(F)(F)F)(F)F Chemical compound C(=O)OC(C)C.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)C)C=C(C1)C(F)(F)F)(F)F XCFFKUNKGYHDDH-CVJFODCESA-N 0.000 description 1
- DPHCOSDQBNILIT-HLRBRJAUSA-N C(=O)OC(C)C.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)C2CC2)C=C(C1)C(F)(F)F)(F)F Chemical compound C(=O)OC(C)C.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)C2CC2)C=C(C1)C(F)(F)F)(F)F DPHCOSDQBNILIT-HLRBRJAUSA-N 0.000 description 1
- FTLSHYUKEKAOKK-UHFFFAOYSA-N C(=O)OC(C)C.N1=CC=CC2=CC=CC=C12 Chemical compound C(=O)OC(C)C.N1=CC=CC2=CC=CC=C12 FTLSHYUKEKAOKK-UHFFFAOYSA-N 0.000 description 1
- YNMOYPNGNOEMIP-VNUWRVCDSA-N C(=O)OC(C)C.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)C Chemical compound C(=O)OC(C)C.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)C YNMOYPNGNOEMIP-VNUWRVCDSA-N 0.000 description 1
- GXBRAGIYFSKPPR-SCYNACPDSA-N C(=O)OC(C)C.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)CC Chemical compound C(=O)OC(C)C.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)CC GXBRAGIYFSKPPR-SCYNACPDSA-N 0.000 description 1
- MODIOHPNGCFKMI-HLRBRJAUSA-N C(=O)OCC.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)C2CC2)C=C(C1)C(F)(F)F)(F)F Chemical compound C(=O)OCC.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)C2CC2)C=C(C1)C(F)(F)F)(F)F MODIOHPNGCFKMI-HLRBRJAUSA-N 0.000 description 1
- QJHCUDIRGAVPMY-CFILVAQYSA-N C(=O)OCC.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)CC)C=C(C1)C(F)(F)F)(F)F Chemical compound C(=O)OCC.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)CC)C=C(C1)C(F)(F)F)(F)F QJHCUDIRGAVPMY-CFILVAQYSA-N 0.000 description 1
- FTHSVDNBSQPLIM-JGAZGGJJSA-N C(=O)OCC.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)C1CC1 Chemical compound C(=O)OCC.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)C1CC1 FTHSVDNBSQPLIM-JGAZGGJJSA-N 0.000 description 1
- STBIXBZBMAPKDY-SCYNACPDSA-N C(=O)OCC.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)CC Chemical compound C(=O)OCC.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)CC STBIXBZBMAPKDY-SCYNACPDSA-N 0.000 description 1
- DZXMFGUBLHVKQS-HLRBRJAUSA-N C(=O)OCCC.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)C2CC2)C=C(C1)C(F)(F)F)(F)F Chemical compound C(=O)OCCC.FC(C=1C=C(CN[C@H]2C[C@H](NC3=CC=C(C=C23)C(F)(F)F)C2CC2)C=C(C1)C(F)(F)F)(F)F DZXMFGUBLHVKQS-HLRBRJAUSA-N 0.000 description 1
- MMIXTELFENPEOX-VNUWRVCDSA-N C(=O)OCCC.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)C Chemical compound C(=O)OCCC.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)C MMIXTELFENPEOX-VNUWRVCDSA-N 0.000 description 1
- SDLWKCKNJUYGTL-JGAZGGJJSA-N C(=O)OCCC.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)C1CC1 Chemical compound C(=O)OCCC.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)C1CC1 SDLWKCKNJUYGTL-JGAZGGJJSA-N 0.000 description 1
- PTBNZFZRLVJHRY-UHFFFAOYSA-N C(C)(C)OC(C(C(OOCCC(C)C)(OCCCCC)OC(C)(C)C)(C)C)(OCC(C)C)OCCCC Chemical compound C(C)(C)OC(C(C(OOCCC(C)C)(OCCCCC)OC(C)(C)C)(C)C)(OCC(C)C)OCCCC PTBNZFZRLVJHRY-UHFFFAOYSA-N 0.000 description 1
- SIGZCAWILVZVRO-UHFFFAOYSA-N CC(=O)C(CN1CCC2=C(C1)C=CC(=C2)N)N Chemical compound CC(=O)C(CN1CCC2=C(C1)C=CC(=C2)N)N SIGZCAWILVZVRO-UHFFFAOYSA-N 0.000 description 1
- 101150069040 CETP gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 239000004381 Choline salt Substances 0.000 description 1
- 108010004103 Chylomicrons Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- RBKAVHRBHKTUKM-UHFFFAOYSA-N ClCCl.CN(CCCN=C=NCC)C Chemical compound ClCCl.CN(CCCN=C=NCC)C RBKAVHRBHKTUKM-UHFFFAOYSA-N 0.000 description 1
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH 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)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-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
- 108020004414 DNA Proteins 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
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108010022535 Farnesyl-Diphosphate Farnesyltransferase Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 229940122498 Gene expression inhibitor Drugs 0.000 description 1
- 206010064571 Gene mutation Diseases 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
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 206010018473 Glycosuria Diseases 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 108010064635 HDL cholesteryl ester Proteins 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 101000889990 Homo sapiens Apolipoprotein(a) Proteins 0.000 description 1
- 101000880514 Homo sapiens Cholesteryl ester transfer protein Proteins 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical class CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
- 239000002841 Lewis acid Substances 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 206010026865 Mass Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 125000005850 N-(alkoxycarbonyl)aminomethyl group Chemical group 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- 238000012565 NMR experiment Methods 0.000 description 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 1
- JBZRLVKMCLOFLG-UHFFFAOYSA-N O=S=Cl Chemical compound O=S=Cl JBZRLVKMCLOFLG-UHFFFAOYSA-N 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000004353 Polyethylene glycol 8000 Substances 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000004280 Sodium formate Substances 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 244000300264 Spinacia oleracea Species 0.000 description 1
- 235000009337 Spinacia oleracea Nutrition 0.000 description 1
- 108020003891 Squalene monooxygenase Proteins 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 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
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- RNFJXKZHLUDESJ-UHFFFAOYSA-N [O].C(CCCCC)OCCCCCCC Chemical compound [O].C(CCCCC)OCCCCCCC RNFJXKZHLUDESJ-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 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
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000005206 alkoxycarbonyloxymethyl group Chemical group 0.000 description 1
- 125000005234 alkyl aluminium group Chemical group 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000000489 anti-atherogenic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003579 anti-obesity Effects 0.000 description 1
- 239000003529 anticholesteremic agent Substances 0.000 description 1
- 229940127226 anticholesterol agent Drugs 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 230000000923 atherogenic effect Effects 0.000 description 1
- 230000000386 athletic effect Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 125000005604 azodicarboxylate group Chemical group 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical class C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- OCBHHZMJRVXXQK-UHFFFAOYSA-M benzyl-dimethyl-tetradecylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 OCBHHZMJRVXXQK-UHFFFAOYSA-M 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
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000002902 bimodal effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000003152 bradykinin antagonist Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229940006460 bromide ion Drugs 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 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
- 159000000007 calcium salts Chemical class 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000005854 carbamoyl-(C1-C2)alkyl group Chemical group 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 235000019417 choline salt Nutrition 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 125000000259 cinnolinyl group Chemical class N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- CHVJITGCYZJHLR-UHFFFAOYSA-N cyclohepta-1,3,5-triene Chemical compound C1C=CC=CC=C1 CHVJITGCYZJHLR-UHFFFAOYSA-N 0.000 description 1
- IROJHXGRCUGUIZ-UHFFFAOYSA-N cyclohexene;ethanol Chemical compound CCO.C1CCC=CC1 IROJHXGRCUGUIZ-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- URYYVOIYTNXXBN-UPHRSURJSA-N cyclooctene Chemical compound C1CCC\C=C/CC1 URYYVOIYTNXXBN-UPHRSURJSA-N 0.000 description 1
- 239000004913 cyclooctene Substances 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical class C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- QMMLUKRVXWXKSI-UHFFFAOYSA-J dichloromethane;titanium(4+);tetrachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Ti+4].ClCCl QMMLUKRVXWXKSI-UHFFFAOYSA-J 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- QMMFVYPAHWMCMS-UHFFFAOYSA-N dimethylsulfide Substances CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical group SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 150000002084 enol ethers Chemical class 0.000 description 1
- 150000002169 ethanolamines Chemical class 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- BHQZJTPHGHVHEO-UHFFFAOYSA-N ethyl cyclopenta[g]quinoline-1-carboxylate Chemical compound C1=C2C=CC=C2C=C2N(C(=O)OCC)C=CC=C21 BHQZJTPHGHVHEO-UHFFFAOYSA-N 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- KSMAEOWGOVHBPP-VNUWRVCDSA-N ethyl formate (2R,4S)-2-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydroquinolin-4-amine Chemical compound C(=O)OCC.N[C@H]1C[C@H](NC2=CC=C(C=C12)C(F)(F)F)C KSMAEOWGOVHBPP-VNUWRVCDSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 150000002221 fluorine Chemical class 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000003844 furanonyl group Chemical group 0.000 description 1
- JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- PYGSKMBEVAICCR-UHFFFAOYSA-N hexa-1,5-diene Chemical group C=CCCC=C PYGSKMBEVAICCR-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- BMVXCPBXGZKUPN-UHFFFAOYSA-O hexylazanium Chemical compound CCCCCC[NH3+] BMVXCPBXGZKUPN-UHFFFAOYSA-O 0.000 description 1
- 102000052454 human CETP Human genes 0.000 description 1
- 102000045903 human LPA Human genes 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 210000003090 iliac artery Anatomy 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 229940028435 intralipid Drugs 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 229940006461 iodide ion Drugs 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 125000000686 lactone group Chemical group 0.000 description 1
- 238000007273 lactonization reaction Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- XHXXWWGGXFUMAJ-UHFFFAOYSA-N methanethiol;sodium Chemical compound [Na].SC XHXXWWGGXFUMAJ-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000005858 morpholino(C2-C3)alkyl group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- XXZNFWHGOMHWCO-UHFFFAOYSA-N n,n-diethylthiohydroxylamine Chemical compound CCN(S)CC XXZNFWHGOMHWCO-UHFFFAOYSA-N 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
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- CQDAMYNQINDRQC-UHFFFAOYSA-N oxatriazole Chemical compound C1=NN=NO1 CQDAMYNQINDRQC-UHFFFAOYSA-N 0.000 description 1
- ATYBXHSAIOKLMG-UHFFFAOYSA-N oxepin Chemical compound O1C=CC=CC=C1 ATYBXHSAIOKLMG-UHFFFAOYSA-N 0.000 description 1
- 150000002921 oxetanes Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 125000005856 piperidino(C2-C3)alkyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 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
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940085678 polyethylene glycol 8000 Drugs 0.000 description 1
- 235000019446 polyethylene glycol 8000 Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000004309 pyranyl group Chemical class O1C(C=CC=C1)* 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005857 pyrrolidino(C2-C3)alkyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].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 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- AZAKMLHUDVIDFN-UHFFFAOYSA-N tert-butyl nitrate Chemical compound CC(C)(C)O[N+]([O-])=O AZAKMLHUDVIDFN-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 235000015149 toffees Nutrition 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000002054 transplantation Methods 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
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- AWSFICBXMUKWSK-UHFFFAOYSA-N ytterbium(3+) Chemical compound [Yb+3] AWSFICBXMUKWSK-UHFFFAOYSA-N 0.000 description 1
- 229930188494 zaragozic acid Natural products 0.000 description 1
- DFKDOZMCHOGOBR-UHFFFAOYSA-N zaragozic acid A Natural products O1C(C(O)(C(O2)C(O)=O)C(O)=O)(C(O)=O)C(OC(=O)C=CC(C)CC(C)CC)C(O)C21CCC(=C)C(OC(C)=O)C(C)CC1=CC=CC=C1 DFKDOZMCHOGOBR-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with 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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with 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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- C07D215/46—Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/16—Ring systems of three rings containing carbocyclic rings other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10092798P | 1998-09-17 | 1998-09-17 | |
| US60/100,927 | 1998-09-17 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99811014A Division CN1318057A (zh) | 1998-09-17 | 1999-09-10 | 用作cetp抑制剂的4－氨基取代的－2－取代的－1,2,3,4－四氢喹啉 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1515259A true CN1515259A (zh) | 2004-07-28 |
Family
ID=22282246
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99811014A Pending CN1318057A (zh) | 1998-09-17 | 1999-09-10 | 用作cetp抑制剂的4－氨基取代的－2－取代的－1,2,3,4－四氢喹啉 |
| CNA2004100049599A Pending CN1515259A (zh) | 1998-09-17 | 1999-09-10 | 用作cetp抑制剂的4-氨基取代的-2-取代的-1，2，3，4-四氢喹啉 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99811014A Pending CN1318057A (zh) | 1998-09-17 | 1999-09-10 | 用作cetp抑制剂的4－氨基取代的－2－取代的－1,2,3,4－四氢喹啉 |
Country Status (50)
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008083551A1 (en) * | 2007-01-12 | 2008-07-17 | Shanghai Institute Of Pharmaceutical Industry | 4-substituted oxyphenyl quinolines, intermediate compounds, preparation methods and uses thereof |
| CN101212966B (zh) * | 2005-07-01 | 2012-03-14 | 默沙东公司 | 合成cetp抑制剂的方法 |
Families Citing this family (128)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6197786B1 (en) * | 1998-09-17 | 2001-03-06 | Pfizer Inc | 4-Carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines |
| US6147089A (en) * | 1998-09-17 | 2000-11-14 | Pfizer Inc. | Annulated 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines |
| GT199900147A (es) * | 1998-09-17 | 1999-09-06 | 1, 2, 3, 4- tetrahidroquinolinas 2-sustituidas 4-amino sustituidas. | |
| US7115279B2 (en) | 2000-08-03 | 2006-10-03 | Curatolo William J | Pharmaceutical compositions of cholesteryl ester transfer protein inhibitors |
| US20060287254A1 (en) * | 2001-01-26 | 2006-12-21 | Schering Corporation | Use of substituted azetidinone compounds for the treatment of sitosterolemia |
| SE0101161D0 (sv) | 2001-03-30 | 2001-03-30 | Astrazeneca Ab | New compounds |
| WO2002087556A2 (en) * | 2001-04-11 | 2002-11-07 | Atherogenics, Inc. | Probucol monoesters and their use to increase plasma hdl cholesterol levels and improve hdl functionality |
| CZ20032898A3 (cs) | 2001-04-30 | 2004-07-14 | Pfizer Products Inc. | Způsob výroby inhibitorů CETP |
| JP2005500314A (ja) * | 2001-06-21 | 2005-01-06 | ファイザー・プロダクツ・インク | コレステロールエステル転送蛋白インヒビターの自己乳化性製剤 |
| ES2333645T3 (es) * | 2001-06-22 | 2010-02-25 | Bend Research, Inc. | Composiciones farmaceuticas de dispersiones de medicamentos y polimeros neutros. |
| CA2448825C (en) * | 2001-06-22 | 2009-08-11 | Pfizer Products Inc. | Pharmaceutical compositions of adsorbates of amorphous drug |
| EP1269994A3 (en) | 2001-06-22 | 2003-02-12 | Pfizer Products Inc. | Pharmaceutical compositions comprising drug and concentration-enhancing polymers |
| BR0215240A (pt) * | 2001-12-19 | 2004-10-26 | Atherogenics Inc | Derivados de calcona e seu uso no tratamento de doenças |
| AU2002361811A1 (en) | 2001-12-19 | 2003-07-09 | Atherogenics, Inc. | 1,3-bis-(substituted-phenyl)-2-propyn-1-ones and their use to treat disorders |
| BR0215212A (pt) * | 2001-12-21 | 2004-12-07 | Novo Nordisk As | Ativador de carboxamida ou sulfonamida de glicoquinase, composto, composição farmacêutica, e, uso de um composto |
| JP4865989B2 (ja) * | 2002-02-01 | 2012-02-01 | ベンド・リサーチ・インコーポレーテッド | 改良された噴霧乾燥装置を使用する均質な噴霧乾燥された固体の非晶質薬物分散物を製造する方法 |
| AR038375A1 (es) | 2002-02-01 | 2005-01-12 | Pfizer Prod Inc | Composiciones farmaceuticas de inhibidores de la proteina de transferencia de esteres de colesterilo |
| ES2305434T3 (es) | 2002-02-01 | 2008-11-01 | Pfizer Products Inc. | Composiciones framaceuticas de dispersiones amorfas de farmacos y materiales que forman microfases lipofilas. |
| JP2005522424A (ja) * | 2002-02-01 | 2005-07-28 | ファイザー・プロダクツ・インク | コレステリルエステル転移タンパク質インヒビターの制御放出性薬剤投与形態 |
| EP1531815B1 (en) * | 2002-06-27 | 2014-09-24 | Novo Nordisk A/S | Glucokinase activators |
| US7071210B2 (en) * | 2002-07-02 | 2006-07-04 | Pfizer Inc. | CETP inhibitors in combination with antihypertensive agents and uses thereof |
| US20040053842A1 (en) * | 2002-07-02 | 2004-03-18 | Pfizer Inc. | Methods of treatment with CETP inhibitors and antihypertensive agents |
| US20090181966A1 (en) * | 2002-10-04 | 2009-07-16 | Millennium Pharmaceuticals, Inc. | PGD2 receptor antagonists for the treatment of inflammatory diseases |
| US7504508B2 (en) | 2002-10-04 | 2009-03-17 | Millennium Pharmaceuticals, Inc. | PGD2 receptor antagonists for the treatment of inflammatory diseases |
| EP1556047A4 (en) | 2002-10-04 | 2009-09-30 | Millennium Pharm Inc | ANTAGONISTS AGAINST THE PGD2 RECEPTOR FOR THE TREATMENT OF INFLAMMATORY DISEASES |
| MXPA05003660A (es) * | 2002-10-21 | 2005-06-08 | Warner Lambert Co | Derivados de quinolina como antagonistas de crth2. |
| JPWO2004052863A1 (ja) * | 2002-12-06 | 2006-04-13 | 協和醗酵工業株式会社 | 抗炎症剤 |
| WO2004056727A2 (en) * | 2002-12-19 | 2004-07-08 | Atherogenics, Inc. | Process of making chalcone derivatives |
| US20040132771A1 (en) * | 2002-12-20 | 2004-07-08 | Pfizer Inc | Compositions of choleseteryl ester transfer protein inhibitors and HMG-CoA reductase inhibitors |
| ATE407670T1 (de) | 2002-12-20 | 2008-09-15 | Pfizer Prod Inc | Dosierungsform enthaltend einen cetp-hemmer und einen hmg-coa reduktase hemmer |
| EP1435356A1 (en) * | 2003-01-06 | 2004-07-07 | Warner-Lambert Company LLC | Quinoline derivatives as CRTH2 antagonists |
| WO2004072042A2 (en) * | 2003-02-12 | 2004-08-26 | Carex S.A. | Quinoline derivative and their use for modulation of lxr activity |
| JP5546715B2 (ja) * | 2003-03-17 | 2014-07-09 | 日本たばこ産業株式会社 | Ｃｅｔｐ阻害剤の医薬組成物 |
| WO2004082675A1 (en) * | 2003-03-17 | 2004-09-30 | Japan Tobacco Inc. | Method for increasing the oral bioavailability of s-[2- ([[1- (2-ethylbutyl) cyclohexyl] carbonyl] amino) phenyl] 2-methylpropanethioate |
| US20040204450A1 (en) * | 2003-03-28 | 2004-10-14 | Pfizer Inc | Quinoline and quinoxaline compounds |
| CN1795177A (zh) * | 2003-03-28 | 2006-06-28 | 辉瑞产品公司 | 作为治疗动脉粥样硬化和肥胖症的cetp抑制剂的 1 , 2 , 4 , －取代的1，2，3，4，－四氢－和1，2二氢－喹啉以及1， 2 , 3 ， 4－四氢－喹喔啉衍生物 |
| TWI494102B (zh) * | 2003-05-02 | 2015-08-01 | Japan Tobacco Inc | 包含ｓ-〔２（〔〔１-（２-乙基丁基）環己基〕羰基〕胺基）苯基〕２-甲基丙烷硫酯及ｈｍｇ輔酶ａ還原酶抑制劑之組合 |
| BRPI0410840A (pt) | 2003-05-30 | 2006-07-04 | Ranbaxy Lab Ltd | derivados substituìdos de pirrol, composição farmacêutica contendo os mesmos e processo para sua preparação |
| CL2004001884A1 (es) | 2003-08-04 | 2005-06-03 | Pfizer Prod Inc | Procedimiento de secado por pulverizacion para la formacion de dispersiones solidas amorfas de un farmaco y polimeros. |
| BRPI0413277A (pt) * | 2003-08-04 | 2006-10-10 | Pfizer Prod Inc | composições farmacêuticas de adsorvatos de medicamentos amorfos e materiais que formam microfases lipofìlicas |
| KR20060080214A (ko) | 2003-09-26 | 2006-07-07 | 니뽄 다바코 산교 가부시키가이샤 | 잔여 리포프로테인 생산 저해 방법 |
| WO2005033082A2 (en) * | 2003-09-30 | 2005-04-14 | Pfizer Products Inc. | Cetp inhibitors and metabolites thereof |
| MXPA06003927A (es) * | 2003-10-08 | 2008-02-07 | Lilly Co Eli | Compuestos y metodos para tratar dislipidemia. |
| ATE428411T1 (de) * | 2003-11-07 | 2009-05-15 | Jj Pharma Inc | Hdl-verstärkende kombinationstherapie-komplexe |
| WO2005066145A1 (en) | 2004-01-06 | 2005-07-21 | Novo Nordisk A/S | Heteroaryl-ureas and their use as glucokinase activators |
| DK1725234T4 (en) | 2004-03-05 | 2016-05-09 | Univ Pennsylvania | METHODS OF TREATING DISEASES OR DISEASES CONNECTED WITH HYPERLIPIDEMIA AND HYPERCOLESTEROLYMIA WITH MINIMIZATION OF SIDE EFFECTS |
| US7262318B2 (en) * | 2004-03-10 | 2007-08-28 | Pfizer, Inc. | Substituted heteroaryl- and phenylsulfamoyl compounds |
| ATE433984T1 (de) | 2004-03-26 | 2009-07-15 | Lilly Co Eli | Verbindungen und verfahren zur behandlung von dyslipidämie |
| MY139887A (en) * | 2004-04-02 | 2009-11-30 | Mitsubishi Tanabe Pharma Corp | Tetrahydronaphthyridine derivatives and a process for preparing the same. |
| UA90269C2 (ru) * | 2004-04-02 | 2010-04-26 | Мицубиси Танабе Фарма Корпорейшн | Тетрагидрохинолиновые производные и способ их получения |
| WO2006009819A1 (en) * | 2004-06-18 | 2006-01-26 | Array Biopharma Inc. | Inhibitors of cholesteryl ester transfer protien |
| EA200700119A1 (ru) * | 2004-06-24 | 2007-10-26 | Эли Лилли Энд Компани | Соединения и способы лечения дислипидемии |
| KR100859223B1 (ko) * | 2004-06-24 | 2008-09-18 | 일라이 릴리 앤드 캄파니 | 이상지혈증 치료를 위한 화합물 및 방법 |
| US20060063828A1 (en) * | 2004-06-28 | 2006-03-23 | Weingarten M D | 1,2-Bis-(substituted-phenyl)-2-propen-1-ones and pharmaceutical compositions thereof |
| US20050288340A1 (en) * | 2004-06-29 | 2005-12-29 | Pfizer Inc | Substituted heteroaryl- and phenylsulfamoyl compounds |
| DOP2005000123A (es) | 2004-07-02 | 2011-07-15 | Merck Sharp & Dohme | Inhibidores de cetp |
| EP2404605B1 (en) * | 2004-08-25 | 2015-04-22 | Essentialis, Inc. | Pharmaceutical formulations of potassium ATP channel openers and uses thereof |
| WO2006033004A1 (en) * | 2004-09-23 | 2006-03-30 | Pfizer Products Inc. | Quinoline compounds as cetp inhibitors |
| US20060063803A1 (en) * | 2004-09-23 | 2006-03-23 | Pfizer Inc | 4-Amino substituted-2-substituted-1,2,3,4-tetrahydroquinoline compounds |
| DE602005016009D1 (de) * | 2004-11-23 | 2009-09-24 | Warner Lambert Co | 7-(2h-pyrazol-3-yl)-3,5-dihydroxy-heptansäure-derivate als hmg-co-a-reductase-inhibitoren zur behandlung von lipidemia |
| WO2006069162A1 (en) * | 2004-12-20 | 2006-06-29 | Reddy Us Therapeutics, Inc. | Novel heterocyclic compounds and their pharmaceutical compositions |
| US8604055B2 (en) | 2004-12-31 | 2013-12-10 | Dr. Reddy's Laboratories Ltd. | Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors |
| ES2644450T3 (es) | 2004-12-31 | 2017-11-29 | Dr. Reddy's Laboratories Ltd. | Nuevos derivados de bencilamina como inhibidores de CETP |
| WO2006082518A1 (en) | 2005-02-03 | 2006-08-10 | Pfizer Products Inc. | Pharmaceutical compositions with enhanced performance |
| UA90706C2 (ru) | 2005-02-24 | 2010-05-25 | Милленниум Фармасьютикалз, Инк. | Антагонисты рецептора pgd2 для лечения воспалительных заболеваний |
| WO2006098394A1 (ja) * | 2005-03-14 | 2006-09-21 | Japan Tobacco Inc. | 脂質吸収抑制方法および脂質吸収抑制剤 |
| BRPI0613591A2 (pt) * | 2005-07-08 | 2011-01-18 | Novo Nordisk As | ativadores de dicicloalquil uréia glicocinase |
| ES2382815T3 (es) * | 2005-07-08 | 2012-06-13 | Novo Nordisk A/S | Dicicloalquilcarbamoil ureas como activadores de glucoquinasa |
| EP2377856A1 (en) * | 2005-07-14 | 2011-10-19 | Novo Nordisk A/S | Urea glucokinase activators |
| GT200600381A (es) | 2005-08-25 | 2007-03-28 | Compuestos organicos | |
| JP4531027B2 (ja) * | 2005-09-29 | 2010-08-25 | 田辺三菱製薬株式会社 | 医薬組成物 |
| JP4681526B2 (ja) * | 2005-09-29 | 2011-05-11 | 田辺三菱製薬株式会社 | 医薬組成物 |
| KR20080059233A (ko) | 2005-10-21 | 2008-06-26 | 노파르티스 아게 | 레닌 억제제, 및 항이상지질혈증제 및/또는 항비만제의조합물 |
| EP1948599A1 (en) | 2005-11-08 | 2008-07-30 | Ranbaxy Laboratories Limited | Process for (3r, 5r)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4- [(4-hydroxy methyl phenyl amino) carbonyl]-pyrrol-1-yl]-3, 5-dihydroxy-heptanoic acid hemi calcium salt |
| US7888376B2 (en) | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
| ES2984297T3 (es) | 2006-01-05 | 2024-10-29 | Essentialis Inc | Sales de abertura de canales ATP de potasio y usos de las mismas |
| PE20071025A1 (es) | 2006-01-31 | 2007-10-17 | Mitsubishi Tanabe Pharma Corp | Compuesto amina trisustituido |
| UY30117A1 (es) | 2006-01-31 | 2007-06-29 | Tanabe Seiyaku Co | Compuesto amina trisustituido |
| UY30244A1 (es) | 2006-03-30 | 2007-11-30 | Tanabe Seiyaku Co | Un proceso para preparar derivados de tetrahidroquinolina |
| GB0615670D0 (en) * | 2006-08-07 | 2006-09-13 | Syngenta Participations Ag | Chemical compounds |
| US7750019B2 (en) | 2006-08-11 | 2010-07-06 | Kowa Company, Ltd. | Pyrimidine compound having benzyl(pyridylmethyl)amine structure and medicament comprising the same |
| WO2008045564A2 (en) * | 2006-10-12 | 2008-04-17 | Epix Delaware, Inc. | Carboxamide compounds and their use as antagonists of the chemokine ccr2 receptor |
| WO2008070496A2 (en) | 2006-12-01 | 2008-06-12 | Bristol-Myers Squibb Company | N- ( (3-benzyl) -2, 2- (bis-phenyl) -propan-1-amine derivatives as cetp inhibitors for the treatment of atherosclerosis and cardiovascular diseases |
| US20080161279A1 (en) * | 2006-12-21 | 2008-07-03 | Wisler Gerald L | Methods of Treating Obesity |
| WO2008084043A1 (en) * | 2007-01-09 | 2008-07-17 | Novo Nordisk A/S | Urea glucokinase activators |
| WO2008084044A1 (en) * | 2007-01-11 | 2008-07-17 | Novo Nordisk A/S | Urea glucokinase activators |
| US7790737B2 (en) | 2007-03-13 | 2010-09-07 | Kowa Company, Ltd. | Substituted pyrimidine compounds and their utility as CETP inhibitors |
| CN101679309B (zh) | 2007-04-13 | 2012-02-29 | 兴和株式会社 | 具有二苄胺结构的新型嘧啶化合物和含有该化合物的药物 |
| AU2008272923A1 (en) * | 2007-07-02 | 2009-01-08 | Essentialis, Inc. | Salts of potassium ATP channel openers and uses thereof |
| SI2207775T1 (sl) | 2007-11-05 | 2012-05-31 | Novartis Ag | benzilamino karboksiacil piperidinski derivati kot inhibitorji CETP uporabni za zdravljenje bolezni kot je hiperlipidemija ali arterioskleroza |
| EP2404901B1 (en) | 2007-12-03 | 2013-05-22 | Novartis AG | 1,2-Disubstituted 4-benzylamino-pyrrolidine derivatives as CETP inhibitors useful for the treatment of diseases such as hyperlipidemia or arteriosclerosis |
| JP2011506466A (ja) | 2007-12-11 | 2011-03-03 | 株式会社サイトパスファインダー | カルボキサミド化合物ならびにケモカイン受容体アゴニストとしてのそれらの使用 |
| MX2011012198A (es) | 2009-05-15 | 2011-12-08 | Novartis Ag | Aril-piridinas como inhibidoras de sintasa de aldosterona. |
| KR20120036850A (ko) | 2009-05-15 | 2012-04-18 | 노파르티스 아게 | 알도스테론 신타제 억제제로서의 벤족사졸론 유도체 |
| EA201101672A1 (ru) | 2009-05-28 | 2012-06-29 | Новартис Аг | Замещенные производные аминомасляной кислоты в качестве ингибиторов неприлизина |
| JP5420761B2 (ja) | 2009-05-28 | 2014-02-19 | ノバルティス アーゲー | ネプリリシン阻害剤としての置換アミノプロピオン酸誘導体 |
| TWI450896B (zh) | 2009-06-30 | 2014-09-01 | Lilly Co Eli | 反式－４－〔〔（５ｓ）－５－〔〔〔３，５－雙（三氟甲基）苯基〕甲基〕（２－甲基－２ｈ－四唑－５－基）胺基〕－２，３，４，５－四氫－７，９－二甲基－１ｈ－１－苯并氮呯－１－基〕甲基〕－環己基羧酸 |
| US8519134B2 (en) | 2009-11-17 | 2013-08-27 | Novartis Ag | Aryl-pyridine derivatives as aldosterone synthase inhibitors |
| JO2967B1 (en) | 2009-11-20 | 2016-03-15 | نوفارتس ايه جي | Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors |
| ES2472446T3 (es) | 2009-11-30 | 2014-07-01 | Novartis Ag | Derivados de imidazol como inhibidores de aldosterona sintasa |
| CA2799708A1 (en) | 2010-05-21 | 2011-11-24 | Pfizer Inc. | 2-phenyl benzoylamides |
| US8877815B2 (en) | 2010-11-16 | 2014-11-04 | Novartis Ag | Substituted carbamoylcycloalkyl acetic acid derivatives as NEP |
| US8673974B2 (en) | 2010-11-16 | 2014-03-18 | Novartis Ag | Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors |
| EP2668507B1 (en) | 2011-01-26 | 2017-08-23 | INSERM - Institut National de la Santé et de la Recherche Médicale | Method for assessing a subject's risk of having a cardiovascular disease. |
| WO2012120414A2 (en) | 2011-03-04 | 2012-09-13 | Pfizer Inc. | Edn3-like peptides and uses thereof |
| EA025100B1 (ru) | 2011-06-17 | 2016-11-30 | Мерк Шарп И Доум Корп. | Циклоалкил-конденсированные тетрагидрохинолины в качестве модуляторов рецепторов crth |
| TWI537262B (zh) * | 2011-08-17 | 2016-06-11 | 美國禮來大藥廠 | 供治療糖尿病使用之新穎１，２，３，４－四氫喹啉衍生物 |
| US9199967B2 (en) | 2011-08-18 | 2015-12-01 | Dr. Reddy's Laboratories Ltd. | Substituted heterocyclic amine compounds as cholestryl ester-transfer protein (CETP) inhibitors |
| EP2760864B1 (en) | 2011-09-27 | 2018-01-24 | Dr. Reddy's Laboratories Ltd. | 5-BENZYLAMINOMETHYL-6-AMINOPYRAZOLO[3,4-b]PYRIDINE DERIVATIVES AS CHOLESTERYL ESTER-TRANSFER PROTEIN (CETP) INHIBITORS USEFUL FOR THE TREATMENT OF ATHEROSCLEROSIS |
| MX347400B (es) | 2012-06-29 | 2017-04-18 | Univ Nac Autónoma De México | Vacuna de aplicacion nasal contra el desarrollo de la enfermedad aterosclerotica y el higado graso. |
| UY35144A (es) | 2012-11-20 | 2014-06-30 | Novartis Ag | Miméticos lineales sintéticos de apelina para el tratamiento de insuficiencia cardiaca |
| EP2956464B1 (en) | 2013-02-14 | 2018-03-28 | Novartis AG | Substituted bisphenyl butanoic phosphonic acid derivatives as nep (neutral endopeptidase) inhibitors |
| JP2016516804A (ja) | 2013-04-17 | 2016-06-09 | ファイザー・インク | 心血管疾患を治療するためのｎ−ピペリジン−３−イルベンズアミド誘導体 |
| BR112016001376A2 (pt) | 2013-07-25 | 2017-10-24 | Novartis Ag | bioconjugados de polipeptídeos de apelin sintéticos |
| TW201536814A (zh) | 2013-07-25 | 2015-10-01 | Novartis Ag | 用於治療心臟衰竭之合成環狀多肽 |
| AU2015307306B2 (en) * | 2014-08-28 | 2021-01-21 | Newamsterdam Pharma B.V. | Pharmaceutical composition and therapeutic combination comprising a cholesteryl ester transfer protein inhibitor and HMG CoA reductase inhibitors |
| MX389591B (es) | 2014-08-29 | 2025-03-20 | Tes Pharma S R L | INHIBIDORES DE ACIDO A-AMINO-ß-CARBOXIMUCONICO SEMIALDEHIDO DESCARBOXILASA |
| WO2016055901A1 (en) | 2014-10-08 | 2016-04-14 | Pfizer Inc. | Substituted amide compounds |
| BR112017014194A2 (pt) | 2015-01-23 | 2018-01-09 | Novartis Ag | conjugados de ácido graxo de apelina sintéticos com meia-vida melhorada |
| JOP20190086A1 (ar) | 2016-10-21 | 2019-04-18 | Novartis Ag | مشتقات نافثيريدينون جديدة واستخدامها في معالجة عدم انتظام ضربات القلب |
| UY38072A (es) | 2018-02-07 | 2019-10-01 | Novartis Ag | Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos |
| CA3093025A1 (en) | 2018-06-12 | 2019-12-19 | Vtv Therapeutics Llc | Therapeutic uses of glucokinase activators in combination with insulin or insulin analogs |
| BR112021013807A2 (pt) | 2019-01-18 | 2021-11-30 | Astrazeneca Ab | Inibidores de pcsk9 e seus métodos de uso |
| WO2021167840A1 (en) | 2020-02-18 | 2021-08-26 | Vtv Therapeutics Llc | Sulfoxide and sulfone glucokinase activators and methods of use thereof |
| MX2022015525A (es) | 2020-06-08 | 2023-03-23 | Vtv Therapeutics Llc | Sales o co-cristales del acido {2-[3-ciclohexil-3-(trans-4-propoxi ciclohexil)ureido]tiazol-5-ilsulfanil}acetico y usos de los mismos. |
| MX2023001202A (es) | 2020-07-29 | 2023-02-23 | Amryt Pharmaceuticals Inc | Lomitapida para uso en metodos para tratar la hiperlipidemia e hipercolesterolemia en pacientes pediatricos. |
| AR127698A1 (es) | 2021-11-23 | 2024-02-21 | Novartis Ag | Derivados de naftiridinona para el tratamiento de una enfermedad o un trastorno |
| US20240391941A1 (en) | 2023-05-24 | 2024-11-28 | Novartis Ag | Naphthyridinone derivatives for the treatment of a disease or disorder |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5231102A (en) * | 1989-03-08 | 1993-07-27 | Merck Sharp & Dohme, Ltd. | Tetrahydroquinoline derivatives useful for neurodegenerative disorders |
| US5276168A (en) * | 1990-06-18 | 1994-01-04 | E. R. Squibb & Sons, Inc. | Benzopyran derivatives and heterocyclic analogs thereof as antiischemic agents |
| US5401848A (en) | 1990-11-26 | 1995-03-28 | E. R. Squibb & Sons, Inc. | Indane and quinoline derivatives |
| KR920014799A (ko) * | 1991-01-18 | 1992-08-25 | 나오가따 다이도 | 신규벤조[5,6]시클로헵타[1,2-b]피리딘 유도체 및 이를 함유하는 항알레르기제 |
| US5288725A (en) * | 1992-10-15 | 1994-02-22 | Merck & Co., Inc. | Pyrroloquinoline Bradykinin antagonist |
| HRP970330B1 (en) * | 1996-07-08 | 2004-06-30 | Bayer Ag | Cycloalkano pyridines |
| DE19627431A1 (de) | 1996-07-08 | 1998-01-15 | Bayer Ag | Heterocyclisch kondensierte Pyridine |
| GT199900147A (es) * | 1998-09-17 | 1999-09-06 | 1, 2, 3, 4- tetrahidroquinolinas 2-sustituidas 4-amino sustituidas. | |
| US6147089A (en) | 1998-09-17 | 2000-11-14 | Pfizer Inc. | Annulated 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines |
| WO2000038722A1 (en) | 1998-12-23 | 2000-07-06 | G.D. Searle & Co. | COMBINATIONS OF CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITORS AND HMG CoA REDUCTASE INHIBITORS FOR CARDIOVASCULAR INDICATIONS |
-
1999
- 1999-09-06 GT GT199900147A patent/GT199900147A/es unknown
- 1999-09-07 US US09/391,313 patent/US6140343A/en not_active Expired - Fee Related
- 1999-09-08 PA PA19998481201A patent/PA8481201A1/es unknown
- 1999-09-08 GC GCP1999273 patent/GC0000108A/xx active
- 1999-09-10 EE EEP200100167A patent/EE200100167A/xx unknown
- 1999-09-10 WO PCT/IB1999/001534 patent/WO2000017165A1/en not_active Ceased
- 1999-09-10 CN CN99811014A patent/CN1318057A/zh active Pending
- 1999-09-10 CN CNA2004100049599A patent/CN1515259A/zh active Pending
- 1999-09-10 TW TW088115688A patent/TW502022B/zh not_active IP Right Cessation
- 1999-09-10 AU AU54403/99A patent/AU747715B2/en not_active Ceased
- 1999-09-10 TR TR2001/00780T patent/TR200100780T2/xx unknown
- 1999-09-10 EP EP99940426A patent/EP1114032B1/en not_active Expired - Lifetime
- 1999-09-10 OA OA1200100062A patent/OA11651A/en unknown
- 1999-09-10 UA UA2001031791A patent/UA70960C2/uk unknown
- 1999-09-10 SV SV1999000150A patent/SV1999000150A/es not_active Application Discontinuation
- 1999-09-10 AR ARP990104554A patent/AR030523A1/es active IP Right Grant
- 1999-09-10 SI SI9930595T patent/SI1114032T1/xx unknown
- 1999-09-10 NZ NZ509837A patent/NZ509837A/xx unknown
- 1999-09-10 DE DE69917790T patent/DE69917790T2/de not_active Expired - Fee Related
- 1999-09-10 AP APAP/P/2001/002100A patent/AP1345A/en active
- 1999-09-10 HU HU0103512A patent/HUP0103512A3/hu unknown
- 1999-09-10 KR KR10-2001-7003416A patent/KR100422286B1/ko not_active Expired - Fee Related
- 1999-09-10 PL PL346830A patent/PL198124B1/pl not_active IP Right Cessation
- 1999-09-10 GE GEAP19995804A patent/GEP20032973B/en unknown
- 1999-09-10 HR HR20010200A patent/HRP20010200B1/xx not_active IP Right Cessation
- 1999-09-10 MY MYPI99003926A patent/MY121405A/en unknown
- 1999-09-10 IL IL14138899A patent/IL141388A0/xx not_active IP Right Cessation
- 1999-09-10 SK SK353-2001A patent/SK3532001A3/sk unknown
- 1999-09-10 HK HK02101447.5A patent/HK1039938A1/zh unknown
- 1999-09-10 CZ CZ2001954A patent/CZ2001954A3/cs unknown
- 1999-09-10 CA CA002344248A patent/CA2344248C/en not_active Expired - Fee Related
- 1999-09-10 CO CO99057641A patent/CO5290250A1/es not_active Application Discontinuation
- 1999-09-10 AT AT99940426T patent/ATE268324T1/de not_active IP Right Cessation
- 1999-09-10 PE PE1999000922A patent/PE20001054A1/es not_active Application Discontinuation
- 1999-09-10 YU YU18101A patent/YU18101A/sh unknown
- 1999-09-10 BR BR9913855-7A patent/BR9913855A/pt not_active Application Discontinuation
- 1999-09-10 DK DK99940426T patent/DK1114032T3/da active
- 1999-09-10 ES ES99940426T patent/ES2221420T3/es not_active Expired - Lifetime
- 1999-09-10 EA EA200100249A patent/EA005761B1/ru not_active IP Right Cessation
- 1999-09-10 PT PT99940426T patent/PT1114032E/pt unknown
- 1999-09-10 JP JP2000574075A patent/JP3561474B2/ja not_active Expired - Fee Related
- 1999-09-10 CU CU20010051A patent/CU23053A3/es unknown
- 1999-09-10 ID IDW20010621A patent/ID27838A/id unknown
- 1999-09-13 MA MA25766A patent/MA26689A1/fr unknown
- 1999-09-13 DZ DZ990191A patent/DZ2891A1/xx active
- 1999-09-13 TN TNTNSN99170A patent/TNSN99170A1/fr unknown
-
2000
- 2000-09-27 US US09/671,221 patent/US6489478B1/en not_active Expired - Fee Related
-
2001
- 2001-02-14 CR CR6306A patent/CR6306A/es unknown
- 2001-02-23 IS IS5858A patent/IS2278B/is unknown
- 2001-03-01 ZA ZA200101745A patent/ZA200101745B/en unknown
- 2001-03-16 NO NO20011349A patent/NO319781B1/no not_active IP Right Cessation
- 2001-04-10 BG BG105429A patent/BG65101B1/bg unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101212966B (zh) * | 2005-07-01 | 2012-03-14 | 默沙东公司 | 合成cetp抑制剂的方法 |
| WO2008083551A1 (en) * | 2007-01-12 | 2008-07-17 | Shanghai Institute Of Pharmaceutical Industry | 4-substituted oxyphenyl quinolines, intermediate compounds, preparation methods and uses thereof |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1515259A (zh) | 用作cetp抑制剂的4-氨基取代的-2-取代的-1，2，3，4-四氢喹啉 | |
| CN1318058A (zh) | 用作cetp抑制剂的4－羧基氨基－2－取代的－1,2,3,4－四氢喹啉 | |
| CN1286815C (zh) | 4－苯胺基喹啉－3－甲酰胺类化合物 | |
| CN1021823C (zh) | 治疗哮喘、关节炎等疾病用的取代的苯并二氢吡喃化合物的制品方法 | |
| CN1522249A (zh) | 作为神经肽y受体的配体的喹啉衍生物 | |
| CN1113236A (zh) | 非肽基速激肽受体拮抗剂 | |
| CN1294577A (zh) | 钾通道抑制剂 | |
| CN1096780A (zh) | 含新型四氢异喹啉化合物的治疗剂 | |
| CN1268133A (zh) | 含有稠合环取代基的作为nos抑制剂的2－氨基吡啶 | |
| CN1380289A (zh) | 可抑制ApoB－分泌物/MTP的酰胺 | |
| CN1524852A (zh) | 具有镇痛作用的新化合物 | |
| CN1597667A (zh) | 用作血管生成抑制剂的喹唑啉衍生物 | |
| CN1922169A (zh) | 螺环杂环衍生物及其应用方法 | |
| CN1809565A (zh) | 用于治疗癌症的吡咯并二氢异喹啉 | |
| CN1248259A (zh) | 稠合的哒嗪衍生物、其生产方法和用途 | |
| CN1166639C (zh) | 抗疟的喹啉衍生物，其制备方法及用途 | |
| CN1681788A (zh) | 抑制cox－2的吡啶衍生物 | |
| CN1268120A (zh) | 新型二氢萘化合物及其制备方法 | |
| CN1335777A (zh) | 以NF－κB抑制剂为有效成分的心肌炎、扩张型心肌病和心衰的预防或治疗药 | |
| CN1516693A (zh) | 可用于治疗性功能障碍的苯并咪唑 | |
| CN1036919C (zh) | 吡唑缩合环衍生物，其制造方法及雄性激素抑制剂 | |
| CN1125943A (zh) | 用作抗肿瘤剂的二酰亚胺多环和杂环发色团 | |
| CN1286683A (zh) | 四氢苯并吲哚衍生物 | |
| CN1096781A (zh) | 含有1-(芳烷基-氨烷基)咪唑化合物的治疗剂 | |
| CN1063489A (zh) | 取代的苯并四氢吡啶及有关化合物的制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1064039 Country of ref document: HK |
|
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1064039 Country of ref document: HK |