UA78522C2

UA78522C2 - Benzoxasine and benzothiasine derivatives, method for synthesis thereof and pharmaceutical composition (variants)

Benzoxasine and benzothiasine derivatives, method for synthesis thereof and pharmaceutical composition (variants) Download PDF

Info

Publication number: UA78522C2
Authority: UA; Ukraine
Prior art keywords: dihydro; phenyl; group; zoxazin; propylamino
Prior art date: 2001-10-16

Application number

UA20040402821A

Other languages

English (en)

Ukrainian (uk)

Inventor

Saibal Kumar Das

Guffam Ranga Madhavan

Priority date

2001-10-16

Filing date

2002-10-15

Publication date

2007-04-10

2002-10-15 Application filed filed Critical

2002-10-15 Priority claimed from PCT/IB2002/004275 external-priority patent/WO2003033481A1/en

2007-04-10 Publication of UA78522C2 publication Critical patent/UA78522C2/uk

Links

238000000034 method Methods 0.000 title claims abstract description 60
230000015572 biosynthetic process Effects 0.000 title claims description 98
239000008194 pharmaceutical composition Substances 0.000 title claims description 16
238000003786 synthesis reaction Methods 0.000 title description 80
150000001875 compounds Chemical class 0.000 claims abstract description 326
150000003839 salts Chemical class 0.000 claims abstract description 164
-1 alkyl carboxylic acids Chemical class 0.000 claims abstract description 115
239000012453 solvate Substances 0.000 claims abstract description 28
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 254
125000006308 propyl amino group Chemical group 0.000 claims description 148
125000003118 aryl group Chemical group 0.000 claims description 144
125000000217 alkyl group Chemical group 0.000 claims description 104
125000003710 aryl alkyl group Chemical group 0.000 claims description 95
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 94
229910052739 hydrogen Inorganic materials 0.000 claims description 87
239000001257 hydrogen Substances 0.000 claims description 86
238000006243 chemical reaction Methods 0.000 claims description 74
239000002253 acid Substances 0.000 claims description 64
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 61
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 57
125000000753 cycloalkyl group Chemical group 0.000 claims description 55
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 54
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 53
125000004475 heteroaralkyl group Chemical group 0.000 claims description 51
125000001072 heteroaryl group Chemical group 0.000 claims description 47
235000019260 propionic acid Nutrition 0.000 claims description 44
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 44
239000000243 solution Substances 0.000 claims description 42
238000011282 treatment Methods 0.000 claims description 42
150000002431 hydrogen Chemical class 0.000 claims description 41
229910052736 halogen Inorganic materials 0.000 claims description 37
150000002367 halogens Chemical class 0.000 claims description 37
125000002252 acyl group Chemical group 0.000 claims description 33
125000000623 heterocyclic group Chemical group 0.000 claims description 33
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 30
229910052760 oxygen Inorganic materials 0.000 claims description 30
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 26
239000001301 oxygen Substances 0.000 claims description 26
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
230000009467 reduction Effects 0.000 claims description 23
125000003545 alkoxy group Chemical group 0.000 claims description 22
235000012000 cholesterol Nutrition 0.000 claims description 22
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 22
229910052717 sulfur Inorganic materials 0.000 claims description 22
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 22
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 21
125000004432 carbon atom Chemical group C* 0.000 claims description 21
239000011593 sulfur Substances 0.000 claims description 21
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 19
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 19
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 19
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 18
125000004104 aryloxy group Chemical group 0.000 claims description 18
229910052799 carbon Inorganic materials 0.000 claims description 18
208000008589 Obesity Diseases 0.000 claims description 17
235000020824 obesity Nutrition 0.000 claims description 17
150000003626 triacylglycerols Chemical class 0.000 claims description 17
239000005711 Benzoic acid Substances 0.000 claims description 16
206010022489 Insulin Resistance Diseases 0.000 claims description 16
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 16
125000005842 heteroatom Chemical group 0.000 claims description 16
229910052757 nitrogen Inorganic materials 0.000 claims description 16
239000004475 Arginine Substances 0.000 claims description 15
125000004423 acyloxy group Chemical group 0.000 claims description 15
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 15
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 15
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 15
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical class NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 14
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 14
125000004442 acylamino group Chemical group 0.000 claims description 14
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 14
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 14
150000007513 acids Chemical class 0.000 claims description 13
125000004414 alkyl thio group Chemical group 0.000 claims description 13
208000029078 coronary artery disease Diseases 0.000 claims description 13
201000010099 disease Diseases 0.000 claims description 13
125000005843 halogen group Chemical group 0.000 claims description 13
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
208000031226 Hyperlipidaemia Diseases 0.000 claims description 12
206010020772 Hypertension Diseases 0.000 claims description 12
125000003277 amino group Chemical group 0.000 claims description 12
125000001769 aryl amino group Chemical group 0.000 claims description 11
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 11
208000035475 disorder Diseases 0.000 claims description 11
125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 10
229910019142 PO4 Inorganic materials 0.000 claims description 10
125000001691 aryl alkyl amino group Chemical group 0.000 claims description 10
230000037396 body weight Effects 0.000 claims description 10
235000021317 phosphate Nutrition 0.000 claims description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 9
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 9
229940024606 amino acid Drugs 0.000 claims description 9
235000001014 amino acid Nutrition 0.000 claims description 9
150000001413 amino acids Chemical class 0.000 claims description 9
239000003085 diluting agent Substances 0.000 claims description 9
239000008103 glucose Substances 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
239000003826 tablet Substances 0.000 claims description 9
125000004001 thioalkyl group Chemical group 0.000 claims description 9
SPXOTSHWBDUUMT-UHFFFAOYSA-N 138-42-1 Chemical compound OS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-N 0.000 claims description 8
201000001320 Atherosclerosis Diseases 0.000 claims description 8
208000024172 Cardiovascular disease Diseases 0.000 claims description 8
102000016267 Leptin Human genes 0.000 claims description 8
108010092277 Leptin Proteins 0.000 claims description 8
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Chemical class CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 8
150000001412 amines Chemical class 0.000 claims description 8
125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 8
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 8
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Chemical class CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 8
125000005553 heteroaryloxy group Chemical group 0.000 claims description 8
239000003112 inhibitor Substances 0.000 claims description 8
NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 claims description 8
229940039781 leptin Drugs 0.000 claims description 8
125000002950 monocyclic group Chemical group 0.000 claims description 8
125000004043 oxo group Chemical group O=* 0.000 claims description 8
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 8
239000010452 phosphate Substances 0.000 claims description 8
150000003458 sulfonic acid derivatives Chemical class 0.000 claims description 8
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 8
208000035150 Hypercholesterolemia Diseases 0.000 claims description 7
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 7
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 7
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 7
125000004103 aminoalkyl group Chemical group 0.000 claims description 7
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 7
125000005162 aryl oxy carbonyl amino group Chemical group 0.000 claims description 7
125000004093 cyano group Chemical group *C#N 0.000 claims description 7
125000004663 dialkyl amino group Chemical group 0.000 claims description 7
208000011580 syndromic disease Diseases 0.000 claims description 7
125000000464 thioxo group Chemical group S=* 0.000 claims description 7
208000002705 Glucose Intolerance Diseases 0.000 claims description 6
239000000556 agonist Substances 0.000 claims description 6
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 claims description 6
239000004615 ingredient Substances 0.000 claims description 6
208000017169 kidney disease Diseases 0.000 claims description 6
ULSIYEODSMZIPX-UHFFFAOYSA-N phenylethanolamine Chemical compound NCC(O)C1=CC=CC=C1 ULSIYEODSMZIPX-UHFFFAOYSA-N 0.000 claims description 6
229950006768 phenylethanolamine Drugs 0.000 claims description 6
201000010065 polycystic ovary syndrome Diseases 0.000 claims description 6
230000002265 prevention Effects 0.000 claims description 6
239000002775 capsule Substances 0.000 claims description 5
235000021588 free fatty acids Nutrition 0.000 claims description 5
230000007062 hydrolysis Effects 0.000 claims description 5
238000006460 hydrolysis reaction Methods 0.000 claims description 5
201000009104 prediabetes syndrome Diseases 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
125000000168 pyrrolyl group Chemical group 0.000 claims description 5
239000000725 suspension Substances 0.000 claims description 5
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 4
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 4
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 4
208000002249 Diabetes Complications Diseases 0.000 claims description 4
206010012655 Diabetic complications Diseases 0.000 claims description 4
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 4
206010028980 Neoplasm Diseases 0.000 claims description 4
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 4
208000001132 Osteoporosis Diseases 0.000 claims description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
206010048214 Xanthoma Diseases 0.000 claims description 4
206010048215 Xanthomatosis Diseases 0.000 claims description 4
150000001414 amino alcohols Chemical class 0.000 claims description 4
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 4
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 4
201000011510 cancer Diseases 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 4
201000001421 hyperglycemia Diseases 0.000 claims description 4
ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 claims description 4
239000006188 syrup Substances 0.000 claims description 4
235000020357 syrup Nutrition 0.000 claims description 4
YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 claims description 4
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
206010003210 Arteriosclerosis Diseases 0.000 claims description 3
229920001268 Cholestyramine Polymers 0.000 claims description 3
206010012289 Dementia Diseases 0.000 claims description 3
206010018364 Glomerulonephritis Diseases 0.000 claims description 3
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 3
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 3
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 3
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 3
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
239000004472 Lysine Substances 0.000 claims description 3
206010068871 Myotonic dystrophy Diseases 0.000 claims description 3
206010029164 Nephrotic syndrome Diseases 0.000 claims description 3
206010033645 Pancreatitis Diseases 0.000 claims description 3
201000004681 Psoriasis Diseases 0.000 claims description 3
208000017442 Retinal disease Diseases 0.000 claims description 3
206010038923 Retinopathy Diseases 0.000 claims description 3
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 3
235000004279 alanine Nutrition 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 3
150000003863 ammonium salts Chemical class 0.000 claims description 3
150000008064 anhydrides Chemical group 0.000 claims description 3
208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
235000010323 ascorbic acid Nutrition 0.000 claims description 3
125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 claims description 3
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 3
125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 3
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
230000020411 cell activation Effects 0.000 claims description 3
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 3
229960001231 choline Drugs 0.000 claims description 3
125000004122 cyclic group Chemical group 0.000 claims description 3
210000002889 endothelial cell Anatomy 0.000 claims description 3
206010061989 glomerulosclerosis Diseases 0.000 claims description 3
230000001631 hypertensive effect Effects 0.000 claims description 3
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 3
125000001041 indolyl group Chemical group 0.000 claims description 3
230000004054 inflammatory process Effects 0.000 claims description 3
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 3
229960003105 metformin Drugs 0.000 claims description 3
125000004957 naphthylene group Chemical group 0.000 claims description 3
201000009925 nephrosclerosis Diseases 0.000 claims description 3
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 3
239000000843 powder Substances 0.000 claims description 3
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
238000000926 separation method Methods 0.000 claims description 3
239000004474 valine Substances 0.000 claims description 3
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 2
HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 claims description 2
MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 claims description 2
BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims description 2
229940013085 2-diethylaminoethanol Drugs 0.000 claims description 2
UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical class C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 claims description 2
KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical class OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 claims description 2
JBQWQBSRIAGTJT-UHFFFAOYSA-N 3-ethylmorpholine Chemical compound CCC1COCCN1 JBQWQBSRIAGTJT-UHFFFAOYSA-N 0.000 claims description 2
YLUDSYGJHAQGOD-UHFFFAOYSA-N 3-ethylpiperidine Chemical compound CCC1CCCNC1 YLUDSYGJHAQGOD-UHFFFAOYSA-N 0.000 claims description 2
VYIBCOSBNVFEIW-UHFFFAOYSA-N 3-phenylpropanamide Chemical compound NC(=O)CCC1=CC=CC=C1 VYIBCOSBNVFEIW-UHFFFAOYSA-N 0.000 claims description 2
229920002911 Colestipol Polymers 0.000 claims description 2
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 claims description 2
208000032928 Dyslipidaemia Diseases 0.000 claims description 2
208000030814 Eating disease Diseases 0.000 claims description 2
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 2
208000019454 Feeding and Eating disease Diseases 0.000 claims description 2
239000004471 Glycine Substances 0.000 claims description 2
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims description 2
LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 2
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 2
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 2
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 2
150000000994 L-ascorbates Chemical class 0.000 claims description 2
LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 claims description 2
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 2
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 2
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 2
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 2
LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 claims description 2
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 2
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 2
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 2
208000017170 Lipid metabolism disease Diseases 0.000 claims description 2
UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 claims description 2
AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 2
UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims description 2
BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 claims description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 2
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 2
JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 claims description 2
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 2
239000004473 Threonine Substances 0.000 claims description 2
150000001242 acetic acid derivatives Chemical class 0.000 claims description 2
125000000304 alkynyl group Chemical group 0.000 claims description 2
150000003927 aminopyridines Chemical class 0.000 claims description 2
150000005005 aminopyrimidines Chemical class 0.000 claims description 2
229940049706 benzodiazepine Drugs 0.000 claims description 2
150000001558 benzoic acid derivatives Chemical class 0.000 claims description 2
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 2
229960003237 betaine Drugs 0.000 claims description 2
150000001642 boronic acid derivatives Chemical class 0.000 claims description 2
229960001948 caffeine Drugs 0.000 claims description 2
VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 2
229940075419 choline hydroxide Drugs 0.000 claims description 2
150000001860 citric acid derivatives Chemical class 0.000 claims description 2
GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 claims description 2
229960002604 colestipol Drugs 0.000 claims description 2
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 2
235000018417 cysteine Nutrition 0.000 claims description 2
229960003067 cystine Drugs 0.000 claims description 2
125000005265 dialkylamine group Chemical group 0.000 claims description 2
125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 2
125000004586 dihydrobenzopyranyl group Chemical group O1C(CCC2=C1C=CC=C2)* 0.000 claims description 2
235000014632 disordered eating Nutrition 0.000 claims description 2
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims description 2
229940125753 fibrate Drugs 0.000 claims description 2
229960002442 glucosamine Drugs 0.000 claims description 2
150000002315 glycerophosphates Chemical class 0.000 claims description 2
150000002357 guanidines Chemical class 0.000 claims description 2
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 2
XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 claims description 2
229960002591 hydroxyproline Drugs 0.000 claims description 2
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 2
229960000310 isoleucine Drugs 0.000 claims description 2
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 2
150000002688 maleic acid derivatives Chemical class 0.000 claims description 2
229960003194 meglumine Drugs 0.000 claims description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 2
229930182817 methionine Natural products 0.000 claims description 2
235000001968 nicotinic acid Nutrition 0.000 claims description 2
229960003512 nicotinic acid Drugs 0.000 claims description 2
239000011664 nicotinic acid Substances 0.000 claims description 2
150000002823 nitrates Chemical class 0.000 claims description 2
229960003104 ornithine Drugs 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
230000008289 pathophysiological mechanism Effects 0.000 claims description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 2
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 2
150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 2
FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 claims description 2
229960003912 probucol Drugs 0.000 claims description 2
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 2
229960004919 procaine Drugs 0.000 claims description 2
150000003212 purines Chemical class 0.000 claims description 2
125000003226 pyrazolyl group Chemical group 0.000 claims description 2
150000003873 salicylate salts Chemical class 0.000 claims description 2
229940063673 spermidine Drugs 0.000 claims description 2
150000003890 succinate salts Chemical class 0.000 claims description 2
150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 2
150000003892 tartrate salts Chemical class 0.000 claims description 2
229960004559 theobromine Drugs 0.000 claims description 2
KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 claims description 2
235000019157 thiamine Nutrition 0.000 claims description 2
229960003495 thiamine Drugs 0.000 claims description 2
239000011721 thiamine Substances 0.000 claims description 2
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 claims description 2
125000005270 trialkylamine group Chemical group 0.000 claims description 2
YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 claims description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 2
229960000281 trometamol Drugs 0.000 claims description 2
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 2
LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 claims 3
210000002381 plasma Anatomy 0.000 claims 2
125000004171 alkoxy aryl group Chemical group 0.000 claims 1
125000005125 aryl alkyl amino carbonyl group Chemical group 0.000 claims 1
BQUDLWUEXZTHGM-UHFFFAOYSA-N ethyl propaneperoxoate Chemical compound CCOOC(=O)CC BQUDLWUEXZTHGM-UHFFFAOYSA-N 0.000 claims 1
HVFSJXUIRWUHRG-UHFFFAOYSA-N oic acid Natural products C1CC2C3CC=C4CC(OC5C(C(O)C(O)C(CO)O5)O)CC(O)C4(C)C3CCC2(C)C1C(C)C(O)CC(C)=C(C)C(=O)OC1OC(COC(C)=O)C(O)C(O)C1OC(C(C1O)O)OC(COC(C)=O)C1OC1OC(CO)C(O)C(O)C1O HVFSJXUIRWUHRG-UHFFFAOYSA-N 0.000 claims 1
150000003254 radicals Chemical class 0.000 claims 1
230000009466 transformation Effects 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 99
239000000543 intermediate Substances 0.000 abstract description 13
239000003472 antidiabetic agent Substances 0.000 abstract description 9
238000002360 preparation method Methods 0.000 abstract description 8
230000003178 anti-diabetic effect Effects 0.000 abstract description 6
230000000055 hyoplipidemic effect Effects 0.000 abstract description 6
230000000871 hypocholesterolemic effect Effects 0.000 abstract description 5
238000004519 manufacturing process Methods 0.000 abstract description 5
230000008569 process Effects 0.000 abstract description 4
230000003579 anti-obesity Effects 0.000 abstract description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 389
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 187
235000019439 ethyl acetate Nutrition 0.000 description 131
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 126
239000011541 reaction mixture Substances 0.000 description 95
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 90
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
239000007788 liquid Substances 0.000 description 72
239000002904 solvent Substances 0.000 description 68
239000000126 substance Substances 0.000 description 68
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 59
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 54
239000003054 catalyst Substances 0.000 description 54
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
239000012267 brine Substances 0.000 description 38
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 38
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
239000007787 solid Substances 0.000 description 35
238000004587 chromatography analysis Methods 0.000 description 33
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 30
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
238000005481 NMR spectroscopy Methods 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 25
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
229910052751 metal Inorganic materials 0.000 description 22
239000002184 metal Substances 0.000 description 22
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 21
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 21
239000012044 organic layer Substances 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
229960000583 acetic acid Drugs 0.000 description 19
239000002585 base Substances 0.000 description 19
239000010410 layer Substances 0.000 description 19
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 19
241001465754 Metazoa Species 0.000 description 18
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 17
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
238000010533 azeotropic distillation Methods 0.000 description 17
239000008280 blood Substances 0.000 description 17
210000004369 blood Anatomy 0.000 description 17
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 16
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 16
239000003153 chemical reaction reagent Substances 0.000 description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical class [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 15
241000699670 Mus sp. Species 0.000 description 14
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 14
239000000047 product Substances 0.000 description 14
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 13
238000010992 reflux Methods 0.000 description 13
238000012360 testing method Methods 0.000 description 13
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
150000001483 arginine derivatives Chemical class 0.000 description 11
239000003795 chemical substances by application Substances 0.000 description 11
230000000694 effects Effects 0.000 description 11
229910000027 potassium carbonate Inorganic materials 0.000 description 11
235000011181 potassium carbonates Nutrition 0.000 description 11
238000003756 stirring Methods 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
239000011777 magnesium Substances 0.000 description 10
229910052749 magnesium Inorganic materials 0.000 description 10
159000000003 magnesium salts Chemical class 0.000 description 10
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 10
239000007858 starting material Substances 0.000 description 10
239000007868 Raney catalyst Substances 0.000 description 9
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 9
229910000564 Raney nickel Inorganic materials 0.000 description 9
230000032050 esterification Effects 0.000 description 9
238000005886 esterification reaction Methods 0.000 description 9
PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 9
239000003446 ligand Substances 0.000 description 9
229940040692 lithium hydroxide monohydrate Drugs 0.000 description 9
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 9
230000002829 reductive effect Effects 0.000 description 9
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 8
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
102000004877 Insulin Human genes 0.000 description 8
108090001061 Insulin Proteins 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
229910052772 Samarium Inorganic materials 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
150000001408 amides Chemical class 0.000 description 8
239000003480 eluent Substances 0.000 description 8
YSMNMUQGLPOPBO-UHFFFAOYSA-N ethyl 3-(4-aminophenyl)-2-ethoxypropanoate Chemical compound CCOC(=O)C(OCC)CC1=CC=C(N)C=C1 YSMNMUQGLPOPBO-UHFFFAOYSA-N 0.000 description 8
229940125396 insulin Drugs 0.000 description 8
MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 8
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 8
229910052700 potassium Inorganic materials 0.000 description 8
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 8
KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 description 8
229910001023 sodium amalgam Inorganic materials 0.000 description 8
229910000029 sodium carbonate Inorganic materials 0.000 description 8
235000017550 sodium carbonate Nutrition 0.000 description 8
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
102000004316 Oxidoreductases Human genes 0.000 description 7
108090000854 Oxidoreductases Proteins 0.000 description 7
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 7
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 7
150000004703 alkoxides Chemical class 0.000 description 7
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
238000002425 crystallisation Methods 0.000 description 7
230000008025 crystallization Effects 0.000 description 7
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
229910000041 hydrogen chloride Inorganic materials 0.000 description 7
229910052738 indium Inorganic materials 0.000 description 7
APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 7
229910052987 metal hydride Inorganic materials 0.000 description 7
150000004681 metal hydrides Chemical class 0.000 description 7
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
235000000346 sugar Nutrition 0.000 description 7
229910052718 tin Inorganic materials 0.000 description 7
VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 6
CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 6
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
108010046315 IDL Lipoproteins Proteins 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
150000001298 alcohols Chemical class 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
239000001273 butane Substances 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
239000006184 cosolvent Substances 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
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 6
229910052742 iron Inorganic materials 0.000 description 6
OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 6
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 6
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 6
IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 6
OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
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 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 6
239000011135 tin Substances 0.000 description 6
BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 5
229920002134 Carboxymethyl cellulose Polymers 0.000 description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
102000004895 Lipoproteins Human genes 0.000 description 5
108090001030 Lipoproteins Proteins 0.000 description 5
150000001350 alkyl halides Chemical class 0.000 description 5
CAMXVZOXBADHNJ-UHFFFAOYSA-N ammonium nitrite Chemical compound [NH4+].[O-]N=O CAMXVZOXBADHNJ-UHFFFAOYSA-N 0.000 description 5
239000001768 carboxy methyl cellulose Substances 0.000 description 5
235000010948 carboxy methyl cellulose Nutrition 0.000 description 5
239000008112 carboxymethyl-cellulose Substances 0.000 description 5
239000000969 carrier Substances 0.000 description 5
230000003197 catalytic effect Effects 0.000 description 5
239000012043 crude product Substances 0.000 description 5
UVJHQYIOXKWHFD-UHFFFAOYSA-N cyclohexa-1,4-diene Chemical compound C1C=CCC=C1 UVJHQYIOXKWHFD-UHFFFAOYSA-N 0.000 description 5
206010012601 diabetes mellitus Diseases 0.000 description 5
229940079593 drug Drugs 0.000 description 5
239000003814 drug Substances 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000011737 fluorine Substances 0.000 description 5
229910052731 fluorine Inorganic materials 0.000 description 5
239000000852 hydrogen donor Substances 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
125000001624 naphthyl group Chemical group 0.000 description 5
239000003444 phase transfer catalyst Substances 0.000 description 5
125000003386 piperidinyl group Chemical group 0.000 description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
125000000719 pyrrolidinyl group Chemical group 0.000 description 5
235000010288 sodium nitrite Nutrition 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
RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 4
GTVVZTAFGPQSPC-UHFFFAOYSA-N 4-nitrophenylalanine Chemical compound OC(=O)C(N)CC1=CC=C([N+]([O-])=O)C=C1 GTVVZTAFGPQSPC-UHFFFAOYSA-N 0.000 description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
241000700198 Cavia Species 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 4
108010010234 HDL Lipoproteins Proteins 0.000 description 4
102000015779 HDL Lipoproteins Human genes 0.000 description 4
241000282414 Homo sapiens Species 0.000 description 4
108060001084 Luciferase Proteins 0.000 description 4
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
208000018262 Peripheral vascular disease Diseases 0.000 description 4
KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
108010062497 VLDL Lipoproteins Proteins 0.000 description 4
AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
125000004069 aziridinyl group Chemical group 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
229910000024 caesium carbonate Inorganic materials 0.000 description 4
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 4
239000000920 calcium hydroxide Substances 0.000 description 4
229910001861 calcium hydroxide Inorganic materials 0.000 description 4
238000004296 chiral HPLC Methods 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
238000011161 development Methods 0.000 description 4
230000018109 developmental process Effects 0.000 description 4
UVVCVMAXJFZYTE-UHFFFAOYSA-N ethyl 3-(2-ethoxy-4-nitrophenyl)prop-2-enoate Chemical compound CCOC(=O)C=CC1=CC=C([N+]([O-])=O)C=C1OCC UVVCVMAXJFZYTE-UHFFFAOYSA-N 0.000 description 4
125000004494 ethyl ester group Chemical group 0.000 description 4
125000002541 furyl group Chemical group 0.000 description 4
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 4
229930195733 hydrocarbon Natural products 0.000 description 4
150000002430 hydrocarbons Chemical class 0.000 description 4
239000011630 iodine Substances 0.000 description 4
229910052740 iodine Inorganic materials 0.000 description 4
SPAKMVQVTSVXES-UHFFFAOYSA-N methanol;oxolane;hydrate Chemical compound O.OC.C1CCOC1 SPAKMVQVTSVXES-UHFFFAOYSA-N 0.000 description 4
239000002808 molecular sieve Substances 0.000 description 4
150000007530 organic bases Chemical class 0.000 description 4
125000001979 organolithium group Chemical group 0.000 description 4
150000003003 phosphines Chemical class 0.000 description 4
239000013612 plasmid Substances 0.000 description 4
239000011736 potassium bicarbonate Substances 0.000 description 4
229910000028 potassium bicarbonate Inorganic materials 0.000 description 4
235000015497 potassium bicarbonate Nutrition 0.000 description 4
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
239000004304 potassium nitrite Substances 0.000 description 4
235000010289 potassium nitrite Nutrition 0.000 description 4
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
230000035484 reaction time Effects 0.000 description 4
229910052703 rhodium Inorganic materials 0.000 description 4
239000010948 rhodium Substances 0.000 description 4
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 4
229910052707 ruthenium Inorganic materials 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 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
ZESZRYHGWHGUAX-UHFFFAOYSA-N 2-[2,2-diethylbutylperoxy(hydroxy)phosphoryl]acetic acid Chemical compound CCC(CC)(CC)COOP(O)(=O)CC(O)=O ZESZRYHGWHGUAX-UHFFFAOYSA-N 0.000 description 3
SFWWGMKXCYLZEG-UHFFFAOYSA-N 3-methylmorpholine Chemical compound CC1COCCN1 SFWWGMKXCYLZEG-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
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
241000282412 Homo Species 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
108010007622 LDL Lipoproteins Proteins 0.000 description 3
102000007330 LDL Lipoproteins Human genes 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
208000006011 Stroke Diseases 0.000 description 3
229940100389 Sulfonylurea Drugs 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
150000008051 alkyl sulfates Chemical class 0.000 description 3
239000000883 anti-obesity agent Substances 0.000 description 3
229940125710 antiobesity agent Drugs 0.000 description 3
239000011260 aqueous acid Substances 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
125000004429 atom Chemical group 0.000 description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
238000009835 boiling Methods 0.000 description 3
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 3
ZMCUDHNSHCRDBT-UHFFFAOYSA-M caesium bicarbonate Chemical compound [Cs+].OC([O-])=O ZMCUDHNSHCRDBT-UHFFFAOYSA-M 0.000 description 3
229910000019 calcium carbonate Inorganic materials 0.000 description 3
150000004649 carbonic acid derivatives Chemical class 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
230000001906 cholesterol absorption Effects 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
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 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 3
229940008406 diethyl sulfate Drugs 0.000 description 3
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 3
230000006806 disease prevention Effects 0.000 description 3
229940088598 enzyme Drugs 0.000 description 3
239000012634 fragment Substances 0.000 description 3
230000002068 genetic effect Effects 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
150000004679 hydroxides Chemical class 0.000 description 3
229940126904 hypoglycaemic agent Drugs 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
238000005259 measurement Methods 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
229910000000 metal hydroxide Inorganic materials 0.000 description 3
150000004692 metal hydroxides Chemical class 0.000 description 3
229940098779 methanesulfonic acid Drugs 0.000 description 3
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 3
125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 3
229910017604 nitric acid Inorganic materials 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 3
229910000105 potassium hydride Inorganic materials 0.000 description 3
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 3
238000011084 recovery Methods 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
125000003831 tetrazolyl group Chemical group 0.000 description 3
238000001890 transfection Methods 0.000 description 3
KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
QKZWXPLBVCKXNQ-UHFFFAOYSA-N (2-methoxyphenyl)-[2-[(2-methoxyphenyl)-phenylphosphanyl]ethyl]-phenylphosphane Chemical compound COC1=CC=CC=C1P(C=1C=CC=CC=1)CCP(C=1C(=CC=CC=1)OC)C1=CC=CC=C1 QKZWXPLBVCKXNQ-UHFFFAOYSA-N 0.000 description 2
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
LBCZOTMMGHGTPH-UHFFFAOYSA-N 2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCO)C=C1 LBCZOTMMGHGTPH-UHFFFAOYSA-N 0.000 description 2
MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 description 2
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 2
OKRUMSWHDWKGHA-UHFFFAOYSA-N 5-bromopentanoyl chloride Chemical compound ClC(=O)CCCCBr OKRUMSWHDWKGHA-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
229940123208 Biguanide Drugs 0.000 description 2
230000004568 DNA-binding Effects 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical class OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
206010060378 Hyperinsulinaemia Diseases 0.000 description 2
206010061218 Inflammation Diseases 0.000 description 2
229940122355 Insulin sensitizer Drugs 0.000 description 2
239000005089 Luciferase Substances 0.000 description 2
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
240000004808 Saccharomyces cerevisiae Species 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
229940123464 Thiazolidinedione Drugs 0.000 description 2
108091023040 Transcription factor Proteins 0.000 description 2
102000040945 Transcription factor Human genes 0.000 description 2
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
230000005856 abnormality Effects 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
230000004913 activation Effects 0.000 description 2
210000001789 adipocyte Anatomy 0.000 description 2
230000001270 agonistic effect Effects 0.000 description 2
239000003288 aldose reductase inhibitor Substances 0.000 description 2
229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 2
125000004450 alkenylene group Chemical group 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 2
229960003805 amantadine Drugs 0.000 description 2
238000010171 animal model Methods 0.000 description 2
230000000923 atherogenic effect Effects 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
150000004283 biguanides Chemical class 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
210000005056 cell body Anatomy 0.000 description 2
230000011712 cell development Effects 0.000 description 2
238000012512 characterization method Methods 0.000 description 2
230000003920 cognitive function Effects 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000013256 coordination polymer Substances 0.000 description 2
210000004351 coronary vessel Anatomy 0.000 description 2
125000000000 cycloalkoxy group Chemical group 0.000 description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
125000002704 decyl 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])C([H])([H])C([H])([H])* 0.000 description 2
235000005911 diet Nutrition 0.000 description 2
230000037213 diet Effects 0.000 description 2
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
239000008298 dragée Substances 0.000 description 2
238000001647 drug administration Methods 0.000 description 2
238000001035 drying Methods 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
OYILPGLEYAWUIB-UHFFFAOYSA-N ethyl 3-(4-aminophenyl)-2-propan-2-yloxypropanoate Chemical compound CCOC(=O)C(OC(C)C)CC1=CC=C(N)C=C1 OYILPGLEYAWUIB-UHFFFAOYSA-N 0.000 description 2
239000013604 expression vector Substances 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000013305 food Nutrition 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
230000006870 function Effects 0.000 description 2
230000002496 gastric effect Effects 0.000 description 2
239000008187 granular material Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
230000000260 hypercholesteremic effect Effects 0.000 description 2
230000003451 hyperinsulinaemic effect Effects 0.000 description 2
201000008980 hyperinsulinism Diseases 0.000 description 2
208000006575 hypertriglyceridemia Diseases 0.000 description 2
150000002466 imines Chemical class 0.000 description 2
230000003993 interaction Effects 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
108020001756 ligand binding domains Proteins 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
150000002680 magnesium Chemical class 0.000 description 2
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 2
239000000347 magnesium hydroxide Substances 0.000 description 2
229910001862 magnesium hydroxide Inorganic materials 0.000 description 2
239000000463 material Substances 0.000 description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
IXQSXUPKEHSPQG-UHFFFAOYSA-N methyl 3-(3-amino-2-ethoxyphenyl)prop-2-enoate Chemical compound CCOc1c(N)cccc1C=CC(=O)OC IXQSXUPKEHSPQG-UHFFFAOYSA-N 0.000 description 2
LRYMWBCMNVMSMW-UHFFFAOYSA-N methyl 3-(4-aminophenyl)-2-ethoxypropanoate Chemical compound CCOC(C(=O)OC)CC1=CC=C(N)C=C1 LRYMWBCMNVMSMW-UHFFFAOYSA-N 0.000 description 2
125000002757 morpholinyl group Chemical group 0.000 description 2
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 2
125000001400 nonyl 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])C([H])([H])[H] 0.000 description 2
102000006255 nuclear receptors Human genes 0.000 description 2
108020004017 nuclear receptors Proteins 0.000 description 2
238000005580 one pot reaction Methods 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
125000006678 phenoxycarbonyl group Chemical group 0.000 description 2
125000004193 piperazinyl group Chemical group 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000011877 solvent mixture Substances 0.000 description 2
239000000758 substrate Substances 0.000 description 2
YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
150000001467 thiazolidinediones Chemical class 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
231100000331 toxic Toxicity 0.000 description 2
230000002588 toxic effect Effects 0.000 description 2
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
HXMZJYJOPLEVNU-UHFFFAOYSA-N (2-methoxyphenyl)-[2-(2-methoxyphenyl)phosphanylethyl]phosphane Chemical compound COC1=CC=CC=C1PCCPC1=CC=CC=C1OC HXMZJYJOPLEVNU-UHFFFAOYSA-N 0.000 description 1
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
GTVVZTAFGPQSPC-QMMMGPOBSA-N (2s)-2-azaniumyl-3-(4-nitrophenyl)propanoate Chemical compound OC(=O)[C@@H](N)CC1=CC=C([N+]([O-])=O)C=C1 GTVVZTAFGPQSPC-QMMMGPOBSA-N 0.000 description 1
125000004400 (C1-C12) alkyl group Chemical group 0.000 description 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
125000006530 (C4-C6) alkyl group Chemical group 0.000 description 1
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 1
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
APQIUTYORBAGEZ-UHFFFAOYSA-N 1,1-dibromoethane Chemical compound CC(Br)Br APQIUTYORBAGEZ-UHFFFAOYSA-N 0.000 description 1
QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
SLDQOBRACOQXGE-QPJJXVBHSA-N 1-(4-methoxyphenyl)-1-penten-3-one Chemical compound CCC(=O)\C=C\C1=CC=C(OC)C=C1 SLDQOBRACOQXGE-QPJJXVBHSA-N 0.000 description 1
LSXKDWGTSHCFPP-UHFFFAOYSA-N 1-bromoheptane Chemical compound CCCCCCCBr LSXKDWGTSHCFPP-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
YBONBWJSFMTXLE-UHFFFAOYSA-N 2,3-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(Cl)=C1Cl YBONBWJSFMTXLE-UHFFFAOYSA-N 0.000 description 1
UKHBJYFFALMACQ-UHFFFAOYSA-N 2-(3-benzylphenyl)ethanamine Chemical compound NCCC1=CC=CC(CC=2C=CC=CC=2)=C1 UKHBJYFFALMACQ-UHFFFAOYSA-N 0.000 description 1
GRWKNBPOGBTZMN-UHFFFAOYSA-N 2-benzyl-3-phenylpropane-1,2-diamine Chemical compound C=1C=CC=CC=1CC(N)(CN)CC1=CC=CC=C1 GRWKNBPOGBTZMN-UHFFFAOYSA-N 0.000 description 1
ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 description 1
RUJHATQMIMUYKD-UHFFFAOYSA-N 2-naphthalen-1-ylethanamine Chemical compound C1=CC=C2C(CCN)=CC=CC2=C1 RUJHATQMIMUYKD-UHFFFAOYSA-N 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 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
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
MCNQUWLLXZZZAC-UHFFFAOYSA-N 4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-n-piperidin-1-ylpyrazole-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=C(C#N)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl MCNQUWLLXZZZAC-UHFFFAOYSA-N 0.000 description 1
BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
WNXNUPJZWYOKMW-UHFFFAOYSA-N 5-bromopentanoic acid Chemical compound OC(=O)CCCCBr WNXNUPJZWYOKMW-UHFFFAOYSA-N 0.000 description 1
QQURWFRNETXFTN-UHFFFAOYSA-N 5-fluoro-2-nitrophenol Chemical compound OC1=CC(F)=CC=C1[N+]([O-])=O QQURWFRNETXFTN-UHFFFAOYSA-N 0.000 description 1
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 1
239000005541 ACE inhibitor Substances 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
235000021513 Cinchona Nutrition 0.000 description 1
241000157855 Cinchona Species 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
241000699800 Cricetinae Species 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
239000004366 Glucose oxidase Substances 0.000 description 1
108010015776 Glucose oxidase Proteins 0.000 description 1
206010018429 Glucose tolerance impaired Diseases 0.000 description 1
201000005569 Gout Diseases 0.000 description 1
WJYIASZWHGOTOU-UHFFFAOYSA-N Heptylamine Chemical compound CCCCCCCN WJYIASZWHGOTOU-UHFFFAOYSA-N 0.000 description 1
101000578774 Homo sapiens MAP kinase-activated protein kinase 5 Proteins 0.000 description 1
208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 1
238000004566 IR spectroscopy Methods 0.000 description 1
241001610351 Ipsa Species 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
102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
241000159433 Luma chequen Species 0.000 description 1
102100028396 MAP kinase-activated protein kinase 5 Human genes 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
241000699673 Mesocricetus auratus Species 0.000 description 1
208000001145 Metabolic Syndrome Diseases 0.000 description 1
229910015683 MoOb Inorganic materials 0.000 description 1
LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
108020005497 Nuclear hormone receptor Proteins 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
238000010934 O-alkylation reaction Methods 0.000 description 1
208000002193 Pain Diseases 0.000 description 1
235000021314 Palmitic acid Nutrition 0.000 description 1
208000031481 Pathologic Constriction Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
102000003992 Peroxidases Human genes 0.000 description 1
102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
206010060862 Prostate cancer Diseases 0.000 description 1
208000000236 Prostatic Neoplasms Diseases 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
229940123934 Reductase inhibitor Drugs 0.000 description 1
108091007187 Reductases Proteins 0.000 description 1
241001189372 Satanas Species 0.000 description 1
244000000231 Sesamum indicum Species 0.000 description 1
241001575049 Sonia Species 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
241001455617 Sula Species 0.000 description 1
KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 1
206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 1
238000002441 X-ray diffraction Methods 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000009471 action Effects 0.000 description 1
239000000654 additive Substances 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229930013930 alkaloid Natural products 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
125000004419 alkynylene group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 1
125000002102 aryl alkyloxo group Chemical group 0.000 description 1
125000004350 aryl cycloalkyl group Chemical group 0.000 description 1
125000000732 arylene group Chemical group 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
238000003149 assay kit Methods 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
150000001555 benzenes Chemical group 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
229940073608 benzyl chloride Drugs 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
239000011575 calcium Substances 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
235000019577 caloric intake Nutrition 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
ZJRWDIJRKKXMNW-UHFFFAOYSA-N carbonic acid;cobalt Chemical compound [Co].OC(O)=O ZJRWDIJRKKXMNW-UHFFFAOYSA-N 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
210000001715 carotid artery Anatomy 0.000 description 1
239000004359 castor oil Substances 0.000 description 1
235000019438 castor oil Nutrition 0.000 description 1
230000001364 causal effect Effects 0.000 description 1
230000025084 cell cycle arrest Effects 0.000 description 1
210000001627 cerebral artery Anatomy 0.000 description 1
ABSOMGPQFXJESQ-UHFFFAOYSA-M cesium;hydroxide;hydrate Chemical compound O.[OH-].[Cs+] ABSOMGPQFXJESQ-UHFFFAOYSA-M 0.000 description 1
238000000451 chemical ionisation Methods 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 1
KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
229960004106 citric acid Drugs 0.000 description 1
229910000001 cobalt(II) carbonate Inorganic materials 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
208000026758 coronary atherosclerosis Diseases 0.000 description 1
239000013058 crude material Substances 0.000 description 1
125000002993 cycloalkylene group Chemical group 0.000 description 1
125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 description 1
125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 description 1
KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
238000006264 debenzylation reaction Methods 0.000 description 1
125000003074 decanoyl 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])C([H])([H])C(*)=O 0.000 description 1
206010061428 decreased appetite Diseases 0.000 description 1
230000007547 defect Effects 0.000 description 1
230000008021 deposition Effects 0.000 description 1
230000005595 deprotonation Effects 0.000 description 1
238000010537 deprotonation reaction Methods 0.000 description 1
235000009942 di yu Nutrition 0.000 description 1
244000293080 di yu Species 0.000 description 1
150000008050 dialkyl sulfates Chemical class 0.000 description 1
150000001983 dialkylethers Chemical class 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
238000000113 differential scanning calorimetry Methods 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
238000004821 distillation Methods 0.000 description 1
235000005686 eating Nutrition 0.000 description 1
238000013504 emergency use authorization Methods 0.000 description 1
230000019439 energy homeostasis Effects 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
229960002179 ephedrine Drugs 0.000 description 1
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
KAVCJJPJRSXJDS-UHFFFAOYSA-N ethyl 2-(2-nitrophenoxy)pentanoate Chemical compound CCOC(=O)C(CCC)OC1=CC=CC=C1[N+]([O-])=O KAVCJJPJRSXJDS-UHFFFAOYSA-N 0.000 description 1
NYBPNCZBAGRYQA-UHFFFAOYSA-N ethyl 2-(2-nitrophenoxy)propanoate Chemical compound CCOC(=O)C(C)OC1=CC=CC=C1[N+]([O-])=O NYBPNCZBAGRYQA-UHFFFAOYSA-N 0.000 description 1
VFPRKIHTJUWOIU-UHFFFAOYSA-N ethyl 2-(5-fluoro-2-nitrophenoxy)propanoate Chemical compound CCOC(=O)C(C)OC1=CC(F)=CC=C1[N+]([O-])=O VFPRKIHTJUWOIU-UHFFFAOYSA-N 0.000 description 1
ORSIRXYHFPHWTN-UHFFFAOYSA-N ethyl 2-bromopentanoate Chemical compound CCCC(Br)C(=O)OCC ORSIRXYHFPHWTN-UHFFFAOYSA-N 0.000 description 1
ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
OVQBDRZLOJPPNY-UHFFFAOYSA-N ethyl 3-(4-nitrophenyl)-2-propan-2-yloxypropanoate Chemical compound CCOC(=O)C(OC(C)C)CC1=CC=C([N+]([O-])=O)C=C1 OVQBDRZLOJPPNY-UHFFFAOYSA-N 0.000 description 1
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
PFCHFHIRKBAQGU-UHFFFAOYSA-N ethyl n-propyl ketone Natural products CCCC(=O)CC PFCHFHIRKBAQGU-UHFFFAOYSA-N 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
201000001386 familial hypercholesterolemia Diseases 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
231100000502 fertility decrease Toxicity 0.000 description 1
238000001914 filtration Methods 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000012631 food intake Nutrition 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
235000011389 fruit/vegetable juice Nutrition 0.000 description 1
229940116332 glucose oxidase Drugs 0.000 description 1
235000019420 glucose oxidase Nutrition 0.000 description 1
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
229910003439 heavy metal oxide Inorganic materials 0.000 description 1
125000005349 heteroarylcycloalkyl group Chemical group 0.000 description 1
125000006588 heterocycloalkylene group Chemical group 0.000 description 1
235000012907 honey Nutrition 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
230000003345 hyperglycaemic effect Effects 0.000 description 1
230000000910 hyperinsulinemic effect Effects 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
238000007915 intraurethral administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
230000007794 irritation Effects 0.000 description 1
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
229940011051 isopropyl acetate Drugs 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
229910052808 lithium carbonate Inorganic materials 0.000 description 1
210000001853 liver microsome Anatomy 0.000 description 1
241000238565 lobster Species 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
239000011976 maleic acid Substances 0.000 description 1
229940098895 maleic acid Drugs 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
229940126601 medicinal product Drugs 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
PRRRJIYGXCSGEK-UHFFFAOYSA-N methyl 2-ethoxy-3-(4-formylphenyl)propanoate Chemical compound CCOC(C(=O)OC)CC1=CC=C(C=O)C=C1 PRRRJIYGXCSGEK-UHFFFAOYSA-N 0.000 description 1
GTYSSUMTFAMDFC-UHFFFAOYSA-N methyl 2-ethoxy-3-[3-[(4-hydroxyphenyl)methylamino]phenyl]propanoate Chemical compound CCOC(C(=O)OC)CC1=CC=CC(NCC=2C=CC(O)=CC=2)=C1 GTYSSUMTFAMDFC-UHFFFAOYSA-N 0.000 description 1
HLNLCFFCMIWODT-UHFFFAOYSA-N methyl 3-(3-aminophenyl)-2-ethoxypropanoate Chemical compound CCOC(C(=O)OC)CC1=CC=CC(N)=C1 HLNLCFFCMIWODT-UHFFFAOYSA-N 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
230000003228 microsomal effect Effects 0.000 description 1
230000000877 morphologic effect Effects 0.000 description 1
230000035772 mutation Effects 0.000 description 1
WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 description 1
230000003880 negative regulation of appetite Effects 0.000 description 1
PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
210000002445 nipple Anatomy 0.000 description 1
230000000802 nitrating effect Effects 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
125000006574 non-aromatic ring group Chemical group 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
230000001019 normoglycemic effect Effects 0.000 description 1
125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
239000002674 ointment Substances 0.000 description 1
238000007410 oral glucose tolerance test Methods 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
229940045681 other alkylating agent in atc Drugs 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
230000007310 pathophysiology Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
108040007629 peroxidase activity proteins Proteins 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
BXNHTSHTPBPRFX-UHFFFAOYSA-M potassium nitrite Chemical compound [K+].[O-]N=O BXNHTSHTPBPRFX-UHFFFAOYSA-M 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
238000000634 powder X-ray diffraction Methods 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
238000011552 rat model Methods 0.000 description 1
230000016438 regulation of fat cell differentiation Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
230000004141 reverse cholesterol transport Effects 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
208000031924 shunt primary hyperbilirubinemia Diseases 0.000 description 1
238000010583 slow cooling Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate 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-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000012439 solid excipient Substances 0.000 description 1
238000010532 solid phase synthesis reaction Methods 0.000 description 1
239000004071 soot Substances 0.000 description 1
230000036262 stenosis Effects 0.000 description 1
208000037804 stenosis Diseases 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
KUCOHFSKRZZVRO-UHFFFAOYSA-N terephthalaldehyde Chemical compound O=CC1=CC=C(C=O)C=C1 KUCOHFSKRZZVRO-UHFFFAOYSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
NPDBDJFLKKQMCM-UHFFFAOYSA-N tert-butylglycine Chemical compound CC(C)(C)C(N)C(O)=O NPDBDJFLKKQMCM-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000004149 thio group Chemical group *S* 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
GTZCVFVGUGFEME-HNQUOIGGSA-N trans-aconitic acid Chemical compound OC(=O)C\C(C(O)=O)=C/C(O)=O GTZCVFVGUGFEME-HNQUOIGGSA-N 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
239000012096 transfection reagent Substances 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000013585 weight reducing agent Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1