CA2719288A1

CA2719288A1 - Triazolopyridinone derivatives for use as stearoyl coa desaturase inhibitors

Triazolopyridinone derivatives for use as stearoyl coa desaturase inhibitors Download PDF

Info

Publication number: CA2719288A1
Authority: CA; Canada
Prior art keywords: optionally substituted; compound; dihydro; oxo; alkyl
Prior art date: 2008-04-04
Legal status : Abandoned

Application number

CA2719288A

Other languages

English (en)

French (fr)

Inventor

Dmitry Koltun

Jeff Zablocki

Current Assignee

Gilead Sciences Inc

Original Assignee

Gilead Sciences Inc

Priority date

2008-04-04

Filing date

2009-04-03

Publication date

2009-11-12

2009-04-03 Application filed by Gilead Sciences Inc filed Critical Gilead Sciences Inc

2009-11-12 Publication of CA2719288A1 publication Critical patent/CA2719288A1/en

Status Abandoned legal-status Critical Current

Links

108010087894 Fatty acid desaturases Proteins 0.000 title claims abstract description 69
102000016553 Stearoyl-CoA Desaturase Human genes 0.000 title claims abstract description 67
239000003112 inhibitor Substances 0.000 title claims abstract description 14
LJRXNXBFJXXRNQ-UHFFFAOYSA-N 2h-[1,2,4]triazolo[4,3-a]pyridin-3-one Chemical class C1=CC=CN2C(=O)NN=C21 LJRXNXBFJXXRNQ-UHFFFAOYSA-N 0.000 title abstract description 4
150000001875 compounds Chemical class 0.000 claims abstract description 119
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 57
201000010099 disease Diseases 0.000 claims abstract description 41
208000008589 Obesity Diseases 0.000 claims abstract description 15
235000020824 obesity Nutrition 0.000 claims abstract description 15
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 12
125000000217 alkyl group Chemical group 0.000 claims description 88
125000001424 substituent group Chemical group 0.000 claims description 54
229910052736 halogen Inorganic materials 0.000 claims description 29
150000002367 halogens Chemical class 0.000 claims description 28
239000001257 hydrogen Substances 0.000 claims description 28
229910052739 hydrogen Inorganic materials 0.000 claims description 28
125000002947 alkylene group Chemical group 0.000 claims description 25
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
238000000034 method Methods 0.000 claims description 22
150000002431 hydrogen Chemical group 0.000 claims description 16
150000003839 salts Chemical class 0.000 claims description 14
125000000547 substituted alkyl group Chemical group 0.000 claims description 12
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 12
206010028980 Neoplasm Diseases 0.000 claims description 10
239000008194 pharmaceutical composition Substances 0.000 claims description 10
208000032928 Dyslipidaemia Diseases 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
208000017170 Lipid metabolism disease Diseases 0.000 claims description 8
241000124008 Mammalia Species 0.000 claims description 7
201000011510 cancer Diseases 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
206010022489 Insulin Resistance Diseases 0.000 claims description 6
208000032109 Transient ischaemic attack Diseases 0.000 claims description 6
230000002401 inhibitory effect Effects 0.000 claims description 6
201000010875 transient cerebral ischemia Diseases 0.000 claims description 6
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
DDDARTXFGYJQFS-UHFFFAOYSA-N 2-[(3,4-dichlorophenyl)methyl]-3-oxo-[1,2,4]triazolo[4,3-a]pyridine-6-carboxylic acid Chemical compound O=C1N2C=C(C(=O)O)C=CC2=NN1CC1=CC=C(Cl)C(Cl)=C1 DDDARTXFGYJQFS-UHFFFAOYSA-N 0.000 claims description 5
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 claims description 5
230000003247 decreasing effect Effects 0.000 claims description 5
125000006651 (C3-C20) cycloalkyl group Chemical group 0.000 claims description 4
125000003358 C2-C20 alkenyl group Chemical group 0.000 claims description 4
206010020772 Hypertension Diseases 0.000 claims description 4
150000002148 esters Chemical class 0.000 claims description 4
239000008103 glucose Substances 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 3
JSCHCUAUVSTTPV-UHFFFAOYSA-N 2-[(3,4-dichlorophenyl)methyl]-n-(2-hydroxyethyl)-3-oxo-[1,2,4]triazolo[4,3-a]pyridine-6-carboxamide Chemical compound O=C1N2C=C(C(=O)NCCO)C=CC2=NN1CC1=CC=C(Cl)C(Cl)=C1 JSCHCUAUVSTTPV-UHFFFAOYSA-N 0.000 claims description 3
JDRORHFKYOKHML-UHFFFAOYSA-N 2-[(3,4-dichlorophenyl)methyl]-n-hexyl-3-oxo-[1,2,4]triazolo[4,3-a]pyridine-6-carboxamide Chemical compound O=C1N2C=C(C(=O)NCCCCCC)C=CC2=NN1CC1=CC=C(Cl)C(Cl)=C1 JDRORHFKYOKHML-UHFFFAOYSA-N 0.000 claims description 3
201000001320 Atherosclerosis Diseases 0.000 claims description 3
208000002249 Diabetes Complications Diseases 0.000 claims description 3
206010012655 Diabetic complications Diseases 0.000 claims description 3
208000032382 Ischaemic stroke Diseases 0.000 claims description 3
208000018262 Peripheral vascular disease Diseases 0.000 claims description 3
208000017442 Retinal disease Diseases 0.000 claims description 3
206010038923 Retinopathy Diseases 0.000 claims description 3
208000006011 Stroke Diseases 0.000 claims description 3
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
208000026106 cerebrovascular disease Diseases 0.000 claims description 3
208000029078 coronary artery disease Diseases 0.000 claims description 3
RGMNKANICOKRFW-UHFFFAOYSA-N ethyl 2-[(3,4-dichlorophenyl)methyl]-3-oxo-[1,2,4]triazolo[4,3-a]pyridine-6-carboxylate Chemical compound O=C1N2C=C(C(=O)OCC)C=CC2=NN1CC1=CC=C(Cl)C(Cl)=C1 RGMNKANICOKRFW-UHFFFAOYSA-N 0.000 claims description 3
208000019622 heart disease Diseases 0.000 claims description 3
230000000302 ischemic effect Effects 0.000 claims description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
QSJOHKPAPMCPSV-LBPRGKRZSA-N n-butyl-2-[(1s)-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl]-3-oxo-[1,2,4]triazolo[4,3-a]pyridine-6-carboxamide Chemical compound C1([C@H](C)N2N=C3C=CC(=CN3C2=O)C(=O)NCCCC)=CC=C(F)C(C(F)(F)F)=C1 QSJOHKPAPMCPSV-LBPRGKRZSA-N 0.000 claims description 3
239000000651 prodrug Substances 0.000 claims description 3
229940002612 prodrug Drugs 0.000 claims description 3
HCEBEAXUZILJMF-UHFFFAOYSA-N tert-butyl n-[2-[(3,4-dichlorophenyl)methyl]-3-oxo-[1,2,4]triazolo[4,3-a]pyridin-6-yl]carbamate Chemical compound O=C1N2C=C(NC(=O)OC(C)(C)C)C=CC2=NN1CC1=CC=C(Cl)C(Cl)=C1 HCEBEAXUZILJMF-UHFFFAOYSA-N 0.000 claims description 3
KAQMFLNMRQOAKK-UHFFFAOYSA-N 2-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-3-oxo-[1,2,4]triazolo[4,3-a]pyridine-6-carboxamide Chemical compound O=C1N2C=C(C(=O)N)C=CC2=NN1CC1=CC=C(Cl)C(C(F)(F)F)=C1 KAQMFLNMRQOAKK-UHFFFAOYSA-N 0.000 claims description 2
AGMAOISHIAVAQT-UHFFFAOYSA-N butyl n-[2-[(3,4-dichlorophenyl)methyl]-3-oxo-[1,2,4]triazolo[4,3-a]pyridin-6-yl]carbamate Chemical compound O=C1N2C=C(NC(=O)OCCCC)C=CC2=NN1CC1=CC=C(Cl)C(Cl)=C1 AGMAOISHIAVAQT-UHFFFAOYSA-N 0.000 claims description 2
QRBKGBJKWUCYRX-UHFFFAOYSA-N n-[2-[(3,4-dichlorophenyl)methyl]-3-oxo-[1,2,4]triazolo[4,3-a]pyridin-6-yl]-2,3-dihydroxypropanamide Chemical compound O=C1N2C=C(NC(=O)C(O)CO)C=CC2=NN1CC1=CC=C(Cl)C(Cl)=C1 QRBKGBJKWUCYRX-UHFFFAOYSA-N 0.000 claims description 2
125000006649 (C2-C20) alkynyl group Chemical group 0.000 claims 2
125000003860 C1-C20 alkoxy group Chemical group 0.000 claims 2
ZMLRSVJKJTYXDC-UHFFFAOYSA-N 2-hydroxy-n-[2-[3-(2-methylphenoxy)propyl]-3-oxo-[1,2,4]triazolo[4,3-a]pyridin-6-yl]acetamide Chemical compound CC1=CC=CC=C1OCCCN1C(=O)N2C=C(NC(=O)CO)C=CC2=N1 ZMLRSVJKJTYXDC-UHFFFAOYSA-N 0.000 claims 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
239000012453 solvate Substances 0.000 claims 1
230000001404 mediated effect Effects 0.000 abstract description 14
150000002632 lipids Chemical class 0.000 abstract description 13
208000001145 Metabolic Syndrome Diseases 0.000 abstract description 10
201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 abstract description 9
208000024172 Cardiovascular disease Diseases 0.000 abstract description 6
102000004190 Enzymes Human genes 0.000 abstract description 5
108090000790 Enzymes Proteins 0.000 abstract description 5
230000002159 abnormal effect Effects 0.000 abstract description 3
-1 lipid fatty acid Chemical class 0.000 description 68
125000003118 aryl group Chemical group 0.000 description 52
125000001072 heteroaryl group Chemical group 0.000 description 52
239000000203 mixture Substances 0.000 description 35
125000003545 alkoxy group Chemical group 0.000 description 29
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 23
125000000623 heterocyclic group Chemical group 0.000 description 23
125000002887 hydroxy group Chemical group [H]O* 0.000 description 23
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 22
125000004181 carboxyalkyl group Chemical group 0.000 description 22
125000004093 cyano group Chemical group *C#N 0.000 description 22
125000003342 alkenyl group Chemical group 0.000 description 21
125000000304 alkynyl group Chemical group 0.000 description 20
230000000694 effects Effects 0.000 description 20
150000001412 amines Chemical class 0.000 description 19
125000000753 cycloalkyl group Chemical group 0.000 description 19
125000004432 carbon atom Chemical group C* 0.000 description 18
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 17
125000000392 cycloalkenyl group Chemical group 0.000 description 17
208000035475 disorder Diseases 0.000 description 16
238000002360 preparation method Methods 0.000 description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
235000014113 dietary fatty acids Nutrition 0.000 description 14
239000000194 fatty acid Substances 0.000 description 14
229930195729 fatty acid Natural products 0.000 description 14
150000004665 fatty acids Chemical class 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 12
239000000047 product Substances 0.000 description 12
239000002904 solvent Substances 0.000 description 12
241001465754 Metazoa Species 0.000 description 11
229910052757 nitrogen Inorganic materials 0.000 description 11
238000011282 treatment Methods 0.000 description 11
229910001868 water Inorganic materials 0.000 description 11
125000004414 alkyl thio group Chemical group 0.000 description 10
238000003556 assay Methods 0.000 description 10
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
239000000243 solution Substances 0.000 description 10
238000012360 testing method Methods 0.000 description 10
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
229930194542 Keto Natural products 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
125000002252 acyl group Chemical group 0.000 description 9
125000004442 acylamino group Chemical group 0.000 description 9
125000004423 acyloxy group Chemical group 0.000 description 9
125000005110 aryl thio group Chemical group 0.000 description 9
125000004104 aryloxy group Chemical group 0.000 description 9
125000005553 heteroaryloxy group Chemical group 0.000 description 9
125000000468 ketone group Chemical group 0.000 description 9
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 9
150000003573 thiols Chemical class 0.000 description 9
241000700159 Rattus Species 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
239000004480 active ingredient Substances 0.000 description 8
125000000033 alkoxyamino group Chemical group 0.000 description 8
125000004466 alkoxycarbonylamino group Chemical group 0.000 description 8
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 8
125000004429 atom Chemical group 0.000 description 8
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
125000005843 halogen group Chemical group 0.000 description 8
125000005368 heteroarylthio group Chemical group 0.000 description 8
125000004470 heterocyclooxy group Chemical group 0.000 description 8
125000004468 heterocyclylthio group Chemical group 0.000 description 8
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
125000006598 aminocarbonylamino group Chemical group 0.000 description 7
210000004185 liver Anatomy 0.000 description 7
210000001589 microsome Anatomy 0.000 description 7
239000003960 organic solvent Substances 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
210000001519 tissue Anatomy 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
241000699670 Mus sp. Species 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
108010062497 VLDL Lipoproteins Proteins 0.000 description 6
239000011324 bead Substances 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
239000003814 drug Substances 0.000 description 6
150000002430 hydrocarbons Chemical group 0.000 description 6
239000000463 material Substances 0.000 description 6
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
238000010992 reflux Methods 0.000 description 6
SIARJEKBADXQJG-LFZQUHGESA-N stearoyl-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)CCCCCCCCCCCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 SIARJEKBADXQJG-LFZQUHGESA-N 0.000 description 6
125000003107 substituted aryl group Chemical group 0.000 description 6
239000006228 supernatant Substances 0.000 description 6
239000000725 suspension Substances 0.000 description 6
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
206010019708 Hepatic steatosis Diseases 0.000 description 5
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical group O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 5
239000002253 acid Substances 0.000 description 5
239000012131 assay buffer Substances 0.000 description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
238000004587 chromatography analysis Methods 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
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
238000009472 formulation Methods 0.000 description 5
208000006575 hypertriglyceridemia Diseases 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
229910052760 oxygen Inorganic materials 0.000 description 5
239000001301 oxygen Substances 0.000 description 5
239000002953 phosphate buffered saline Substances 0.000 description 5
229930195734 saturated hydrocarbon Natural products 0.000 description 5
125000005017 substituted alkenyl group Chemical group 0.000 description 5
239000003826 tablet Substances 0.000 description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
229940124597 therapeutic agent Drugs 0.000 description 5
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 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
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
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235000012000 cholesterol Nutrition 0.000 description 4
230000007812 deficiency Effects 0.000 description 4
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 4
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238000001727 in vivo Methods 0.000 description 4
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BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 4
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239000008188 pellet Substances 0.000 description 4
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239000007787 solid Substances 0.000 description 4
125000005346 substituted cycloalkyl group Chemical group 0.000 description 4
239000000758 substrate Substances 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
239000011593 sulfur Substances 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
150000003626 triacylglycerols Chemical class 0.000 description 4
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 4
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
229940123980 Desaturase inhibitor Drugs 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
241000282412 Homo Species 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
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