CZ307784B6 - Inhibitory dipeptidylpeptidázy IV na bázi cyklopropylu kondenzovaného s pyrrolidinem, způsoby jeho přípravy a jejich použití - Google Patents

Info

Publication number

CZ307784B6

CZ307784B6 CZ2014-33A CZ201433A CZ307784B6 CZ 307784 B6 CZ307784 B6 CZ 307784B6 CZ 201433 A CZ201433 A CZ 201433A CZ 307784 B6 CZ307784 B6 CZ 307784B6

Authority

CZ

Czechia

Prior art keywords

inhibitor

agent

compound

formula

carbon atoms

Prior art date

2000-03-10

Links

• Espacenet
• Global Dossier
• Discuss

• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 title claims abstract description 7
• 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 title 1
• 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 title 1
• 239000003112 inhibitor Substances 0.000 claims abstract description 94
• -1 flyburide Chemical compound 0.000 claims abstract description 84
• 239000003472 antidiabetic agent Substances 0.000 claims abstract description 31
• 229940125708 antidiabetic agent Drugs 0.000 claims abstract description 28
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
• 201000010099 disease Diseases 0.000 claims abstract description 22
• 239000003814 drug Substances 0.000 claims abstract description 16
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims abstract description 15
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 15
• 239000000883 anti-obesity agent Substances 0.000 claims abstract description 11
• 229940125710 antiobesity agent Drugs 0.000 claims abstract description 11
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims abstract description 10
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims abstract description 10
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 10
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims abstract description 6
• 229960003105 metformin Drugs 0.000 claims abstract description 5
• 229960005095 pioglitazone Drugs 0.000 claims abstract description 5
• 229960004586 rosiglitazone Drugs 0.000 claims abstract description 5
• GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 claims abstract description 5
• 229960001641 troglitazone Drugs 0.000 claims abstract description 5
• GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 claims abstract description 4
• 150000001875 compounds Chemical class 0.000 claims description 192
• 239000003795 chemical substances by application Substances 0.000 claims description 61
• 125000000217 alkyl group Chemical group 0.000 claims description 56
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 34
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 32
• 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 claims description 18
• 239000001257 hydrogen Substances 0.000 claims description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims description 16
• 150000002632 lipids Chemical class 0.000 claims description 16
• 239000002253 acid Substances 0.000 claims description 12
• 208000011580 syndromic disease Diseases 0.000 claims description 12
• 150000003839 salts Chemical class 0.000 claims description 11
• 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 claims description 10
• 208000008589 Obesity Diseases 0.000 claims description 10
• 235000020824 obesity Nutrition 0.000 claims description 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
• 102000004877 Insulin Human genes 0.000 claims description 9
• 229940125396 insulin Drugs 0.000 claims description 9
• 208000030507 AIDS Diseases 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 208000001132 Osteoporosis Diseases 0.000 claims description 8
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 8
• 239000004059 squalene synthase inhibitor Substances 0.000 claims description 8
• 208000023275 Autoimmune disease Diseases 0.000 claims description 7
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 7
• 108090001061 Insulin Proteins 0.000 claims description 7
• 229940122355 Insulin sensitizer Drugs 0.000 claims description 7
• 206010036049 Polycystic ovaries Diseases 0.000 claims description 7
• 229940100389 Sulfonylurea Drugs 0.000 claims description 7
• 206010003246 arthritis Diseases 0.000 claims description 7
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 7
• 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 7
• ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims description 6
• 201000001320 Atherosclerosis Diseases 0.000 claims description 6
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 6
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 6
• 229940123208 Biguanide Drugs 0.000 claims description 6
• 208000002249 Diabetes Complications Diseases 0.000 claims description 6
• 206010012655 Diabetic complications Diseases 0.000 claims description 6
• 102000004366 Glucosidases Human genes 0.000 claims description 6
• 108010056771 Glucosidases Proteins 0.000 claims description 6
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 6
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 6
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 6
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 6
• 229960005370 atorvastatin Drugs 0.000 claims description 6
• 229960005110 cerivastatin Drugs 0.000 claims description 6
• SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 claims description 6
• 229960003765 fluvastatin Drugs 0.000 claims description 6
• 208000037824 growth disorder Diseases 0.000 claims description 6
• 208000000509 infertility Diseases 0.000 claims description 6
• 230000036512 infertility Effects 0.000 claims description 6
• 231100000535 infertility Toxicity 0.000 claims description 6
• 229960004844 lovastatin Drugs 0.000 claims description 6
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 6
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical group CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims description 6
• 229960001243 orlistat Drugs 0.000 claims description 6
• 230000003647 oxidation Effects 0.000 claims description 6
• 238000007254 oxidation reaction Methods 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 claims description 6
• 229960002965 pravastatin Drugs 0.000 claims description 6
• TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 6
• GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 claims description 6
• 229960002855 simvastatin Drugs 0.000 claims description 6
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 6
• SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 claims description 5
• XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims description 5
• 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 claims description 5
• 206010052779 Transplant rejections Diseases 0.000 claims description 5
• 229960004580 glibenclamide Drugs 0.000 claims description 5
• ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 claims description 5
• 229960001381 glipizide Drugs 0.000 claims description 5
• ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 claims description 5
• 229950004994 meglitinide Drugs 0.000 claims description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 5
• 102000004217 thyroid hormone receptors Human genes 0.000 claims description 5
• 108090000721 thyroid hormone receptors Proteins 0.000 claims description 5
• 238000002054 transplantation Methods 0.000 claims description 5
• XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims description 4
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims description 4
• BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 claims description 4
• ROJNYKZWTOHRNU-UHFFFAOYSA-N 2-chloro-4,5-difluoro-n-[[2-methoxy-5-(methylcarbamoylamino)phenyl]carbamoyl]benzamide Chemical compound CNC(=O)NC1=CC=C(OC)C(NC(=O)NC(=O)C=2C(=CC(F)=C(F)C=2)Cl)=C1 ROJNYKZWTOHRNU-UHFFFAOYSA-N 0.000 claims description 4
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
• 208000000103 Anorexia Nervosa Diseases 0.000 claims description 4
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 4
• HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 claims description 4
• FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 claims description 4
• 208000002705 Glucose Intolerance Diseases 0.000 claims description 4
• 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 4
• 229940086609 Lipase inhibitor Drugs 0.000 claims description 4
• IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 claims description 4
• 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 claims description 4
• 229940123495 Squalene synthetase inhibitor Drugs 0.000 claims description 4
• KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 claims description 4
• 229960002632 acarbose Drugs 0.000 claims description 4
• XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 claims description 4
• 239000000048 adrenergic agonist Substances 0.000 claims description 4
• 229940125709 anorectic agent Drugs 0.000 claims description 4
• 239000002830 appetite depressant Substances 0.000 claims description 4
• 235000014113 dietary fatty acids Nutrition 0.000 claims description 4
• 229960003638 dopamine Drugs 0.000 claims description 4
• 239000000194 fatty acid Substances 0.000 claims description 4
• 229930195729 fatty acid Natural products 0.000 claims description 4
• 150000004665 fatty acids Chemical class 0.000 claims description 4
• 229960003627 gemfibrozil Drugs 0.000 claims description 4
• 229960000346 gliclazide Drugs 0.000 claims description 4
• 201000001421 hyperglycemia Diseases 0.000 claims description 4
• 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 4
• 201000008980 hyperinsulinism Diseases 0.000 claims description 4
• 229960001110 miglitol Drugs 0.000 claims description 4
• PKWDZWYVIHVNKS-UHFFFAOYSA-N netoglitazone Chemical compound FC1=CC=CC=C1COC1=CC=C(C=C(CC2C(NC(=O)S2)=O)C=C2)C2=C1 PKWDZWYVIHVNKS-UHFFFAOYSA-N 0.000 claims description 4
• RHGYHLPFVJEAOC-FFNUKLMVSA-L pitavastatin calcium Chemical compound [Ca+2].[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1.[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 RHGYHLPFVJEAOC-FFNUKLMVSA-L 0.000 claims description 4
• 201000009104 prediabetes syndrome Diseases 0.000 claims description 4
• 229960002354 repaglinide Drugs 0.000 claims description 4
• 229940076279 serotonin Drugs 0.000 claims description 4
• UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 claims description 4
• 229960004425 sibutramine Drugs 0.000 claims description 4
• 229960004394 topiramate Drugs 0.000 claims description 4
• AMNXBQPRODZJQR-DITALETJSA-N (2s)-2-cyclopentyl-2-[3-[(2,4-dimethylpyrido[2,3-b]indol-9-yl)methyl]phenyl]-n-[(1r)-2-hydroxy-1-phenylethyl]acetamide Chemical compound C1([C@@H](C=2C=CC=C(C=2)CN2C3=CC=CC=C3C3=C(C)C=C(N=C32)C)C(=O)N[C@@H](CO)C=2C=CC=CC=2)CCCC1 AMNXBQPRODZJQR-DITALETJSA-N 0.000 claims description 3
• ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 claims description 3
• QBQLYIISSRXYKL-UHFFFAOYSA-N 4-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,2-oxazolidine-3,5-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC1C(=O)NOC1=O QBQLYIISSRXYKL-UHFFFAOYSA-N 0.000 claims description 3
• IETKPTYAGKZLKY-UHFFFAOYSA-N 5-[[4-[(3-methyl-4-oxoquinazolin-2-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N=1C2=CC=CC=C2C(=O)N(C)C=1COC(C=C1)=CC=C1CC1SC(=O)NC1=O IETKPTYAGKZLKY-UHFFFAOYSA-N 0.000 claims description 3
• RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 claims description 3
• 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 claims description 3
• 102000000853 LDL receptors Human genes 0.000 claims description 3
• 108010001831 LDL receptors Proteins 0.000 claims description 3
• 239000000867 Lipoxygenase Inhibitor Substances 0.000 claims description 3
• 229940122142 Lipoxygenase inhibitor Drugs 0.000 claims description 3
• ZPXSCAKFGYXMGA-UHFFFAOYSA-N Mazindol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=C(Cl)C=C1 ZPXSCAKFGYXMGA-UHFFFAOYSA-N 0.000 claims description 3
• 108010014210 axokine Proteins 0.000 claims description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
• 229960001761 chlorpropamide Drugs 0.000 claims description 3
• 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims description 3
• 229960001214 clofibrate Drugs 0.000 claims description 3
• KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 claims description 3
• DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 230000009977 dual effect Effects 0.000 claims description 3
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
• 229960002297 fenofibrate Drugs 0.000 claims description 3
• YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 claims description 3
• 229940125753 fibrate Drugs 0.000 claims description 3
• 230000001771 impaired effect Effects 0.000 claims description 3
• 229950005809 implitapide Drugs 0.000 claims description 3
• 230000002757 inflammatory effect Effects 0.000 claims description 3
• 229960000698 nateglinide Drugs 0.000 claims description 3
• OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 claims description 3
• 229960003562 phentermine Drugs 0.000 claims description 3
• DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 claims description 3
• 229960000395 phenylpropanolamine Drugs 0.000 claims description 3
• 229960002797 pitavastatin Drugs 0.000 claims description 3
• LPYQDDHAJRABQA-UHFFFAOYSA-N 3-(13-hydroxy-10-oxotetradecyl)-5,7-dimethoxy-3h-2-benzofuran-1-one Chemical compound COC1=CC(OC)=CC2=C1C(=O)OC2CCCCCCCCCC(=O)CCC(C)O LPYQDDHAJRABQA-UHFFFAOYSA-N 0.000 claims description 2
• PTQXTEKSNBVPQJ-UHFFFAOYSA-N Avasimibe Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1CC(=O)NS(=O)(=O)OC1=C(C(C)C)C=CC=C1C(C)C PTQXTEKSNBVPQJ-UHFFFAOYSA-N 0.000 claims description 2
• 102400000324 Glucagon-like peptide 1(7-37) Human genes 0.000 claims description 2
• 206010022489 Insulin Resistance Diseases 0.000 claims description 2
• YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 claims description 2
• 108010019598 Liraglutide Proteins 0.000 claims description 2
• 229950010046 avasimibe Drugs 0.000 claims description 2
• 229950010663 balaglitazone Drugs 0.000 claims description 2
• 210000004369 blood Anatomy 0.000 claims description 2
• 239000008280 blood Substances 0.000 claims description 2
• 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 claims description 2
• 235000021588 free fatty acids Nutrition 0.000 claims description 2
• 230000014101 glucose homeostasis Effects 0.000 claims description 2
• 208000006575 hypertriglyceridemia Diseases 0.000 claims description 2
• 208000028774 intestinal disease Diseases 0.000 claims description 2
• 229960002701 liraglutide Drugs 0.000 claims description 2
• 229960003365 mitiglinide Drugs 0.000 claims description 2
• WPGGHFDDFPHPOB-BBWFWOEESA-N mitiglinide Chemical compound C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)O)C1=CC=CC=C1 WPGGHFDDFPHPOB-BBWFWOEESA-N 0.000 claims description 2
• RSGITHTZWHPLBS-QFIPXVFZSA-N n-[4-[2-[[(2s)-3-(6-aminopyridin-3-yl)oxy-2-hydroxypropyl]amino]ethyl]phenyl]-4-propan-2-ylbenzenesulfonamide Chemical compound C1=CC(C(C)C)=CC=C1S(=O)(=O)NC(C=C1)=CC=C1CCNC[C@H](O)COC1=CC=C(N)N=C1 RSGITHTZWHPLBS-QFIPXVFZSA-N 0.000 claims description 2
• 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 claims description 2
• 230000002265 prevention Effects 0.000 claims description 2
• CXGTZJYQWSUFET-IBGZPJMESA-N tesaglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 CXGTZJYQWSUFET-IBGZPJMESA-N 0.000 claims description 2
• 229950004704 tesaglitazar Drugs 0.000 claims description 2
• CMSGWTNRGKRWGS-NQIIRXRSSA-N torcetrapib Chemical compound COC(=O)N([C@H]1C[C@@H](CC)N(C2=CC=C(C=C21)C(F)(F)F)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CMSGWTNRGKRWGS-NQIIRXRSSA-N 0.000 claims description 2
• 229950004514 torcetrapib Drugs 0.000 claims description 2
• QRDSDKAGXMWBID-UHFFFAOYSA-N 5-azabicyclo[3.1.0]hexane Chemical class C1CCN2CC21 QRDSDKAGXMWBID-UHFFFAOYSA-N 0.000 claims 11
• 210000000988 bone and bone Anatomy 0.000 claims 2
• HJCQEONSDMSVQK-QVWGJOIVSA-N (2s)-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-[(4-oxo-4-phenylbutan-2-yl)amino]propanoic acid Chemical compound N([C@@H](CC=1C=CC(OCCC2=C(OC(=N2)C=2C=CC=CC=2)C)=CC=1)C(O)=O)C(C)CC(=O)C1=CC=CC=C1 HJCQEONSDMSVQK-QVWGJOIVSA-N 0.000 claims 1
• 108010036824 Citrate (pro-3S)-lyase Proteins 0.000 claims 1
• 206010029333 Neurosis Diseases 0.000 claims 1
• 229940124754 PPAR-alpha/gamma agonist Drugs 0.000 claims 1
• 229960000583 acetic acid Drugs 0.000 claims 1
• ZZCHHVUQYRMYLW-HKBQPEDESA-N farglitazar Chemical compound N([C@@H](CC1=CC=C(C=C1)OCCC=1N=C(OC=1C)C=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 ZZCHHVUQYRMYLW-HKBQPEDESA-N 0.000 claims 1
• 108010069764 helospectin I Proteins 0.000 claims 1
• HTMVMVKJOPFRMK-OYZAELBCSA-N helospectin i Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=C(O)C=C1 HTMVMVKJOPFRMK-OYZAELBCSA-N 0.000 claims 1
• KRMKZDOWCOBWNU-UHFFFAOYSA-N n-[2,6-di(propan-2-yl)phenyl]-2-tetradecylsulfanylacetamide Chemical compound CCCCCCCCCCCCCCSCC(=O)NC1=C(C(C)C)C=CC=C1C(C)C KRMKZDOWCOBWNU-UHFFFAOYSA-N 0.000 claims 1
• 208000015238 neurotic disease Diseases 0.000 claims 1
• 239000003524 antilipemic agent Substances 0.000 abstract description 15
• 229940124597 therapeutic agent Drugs 0.000 abstract description 7
• XWVHBWQEYOROBE-UHFFFAOYSA-N tridec-2-ene Chemical group CCCCCCCCCCC=CC XWVHBWQEYOROBE-UHFFFAOYSA-N 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 143
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
• 125000004432 carbon atom Chemical group C* 0.000 description 106
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 79
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 71
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
• 239000011541 reaction mixture Substances 0.000 description 59
• 239000000243 solution Substances 0.000 description 56
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
• 239000000203 mixture Substances 0.000 description 51
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
• 235000019439 ethyl acetate Nutrition 0.000 description 38
• 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 description 37
• 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 37
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
• 125000000753 cycloalkyl group Chemical group 0.000 description 34
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 30
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 25
• 125000003118 aryl group Chemical group 0.000 description 25
• 238000007429 general method Methods 0.000 description 25
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 23
• 238000003818 flash chromatography Methods 0.000 description 23
• 239000000047 product Substances 0.000 description 23
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
• 102000001494 Sterol O-Acyltransferase Human genes 0.000 description 21
• 108010054082 Sterol O-acyltransferase Proteins 0.000 description 21
• 125000001072 heteroaryl group Chemical group 0.000 description 21
• 229910052757 nitrogen Inorganic materials 0.000 description 21
• 239000000741 silica gel Substances 0.000 description 21
• 229910002027 silica gel Inorganic materials 0.000 description 21
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
• 238000000034 method Methods 0.000 description 20
• 238000006243 chemical reaction Methods 0.000 description 19
• 239000007787 solid Substances 0.000 description 19
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 17
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
• 239000010410 layer Substances 0.000 description 16
• 230000002829 reductive effect Effects 0.000 description 16
• 125000001424 substituent group Chemical group 0.000 description 16
• 125000003545 alkoxy group Chemical group 0.000 description 15
• 239000012267 brine Substances 0.000 description 15
• 239000000460 chlorine Substances 0.000 description 15
• 229910052938 sodium sulfate Inorganic materials 0.000 description 15
• 235000011152 sodium sulphate Nutrition 0.000 description 15
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 15
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical class CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
• 125000000304 alkynyl group Chemical group 0.000 description 13
• 150000001408 amides Chemical group 0.000 description 13
• 229940024606 amino acid Drugs 0.000 description 13
• 125000003710 aryl alkyl group Chemical group 0.000 description 13
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• 238000000746 purification Methods 0.000 description 12
• 239000002904 solvent Substances 0.000 description 12
• 125000003342 alkenyl group Chemical group 0.000 description 11
• 125000004414 alkyl thio group Chemical group 0.000 description 11
• 150000001413 amino acids Chemical class 0.000 description 11
• 150000002148 esters Chemical class 0.000 description 11
• 125000005842 heteroatom Chemical group 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• 229910052760 oxygen Inorganic materials 0.000 description 11
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 11
• NGJOFQZEYQGZMB-KTKZVXAJSA-N (4S)-5-[[2-[[(2S,3R)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[2-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-2-oxoethyl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-4-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]propanoyl]amino]-5-oxopentanoic acid Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NGJOFQZEYQGZMB-KTKZVXAJSA-N 0.000 description 10
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
• 101800004295 Glucagon-like peptide 1(7-36) Proteins 0.000 description 10
• 229910052786 argon Inorganic materials 0.000 description 10
• 239000003480 eluent Substances 0.000 description 10
• 239000000284 extract Substances 0.000 description 10
• 229910052736 halogen Inorganic materials 0.000 description 10
• 150000002367 halogens Chemical class 0.000 description 10
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 9
• 230000005764 inhibitory process Effects 0.000 description 9
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 8
• 102000004190 Enzymes Human genes 0.000 description 8
• 108090000790 Enzymes Proteins 0.000 description 8
• 102000023984 PPAR alpha Human genes 0.000 description 8
• 108010028924 PPAR alpha Proteins 0.000 description 8
• 150000001412 amines Chemical class 0.000 description 8
• 239000012230 colorless oil Substances 0.000 description 8
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 8
• 235000017557 sodium bicarbonate Nutrition 0.000 description 8
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
• 229910052717 sulfur Chemical group 0.000 description 8
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 7
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
• 102000000536 PPAR gamma Human genes 0.000 description 7
• 108010016731 PPAR gamma Proteins 0.000 description 7
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 7
• 125000004658 aryl carbonyl amino group Chemical group 0.000 description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
• 150000001602 bicycloalkyls Chemical group 0.000 description 7
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 7
• 239000011737 fluorine Substances 0.000 description 7
• 229910052731 fluorine Inorganic materials 0.000 description 7
• 150000002431 hydrogen Chemical class 0.000 description 7
• 238000001727 in vivo Methods 0.000 description 7
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
• 235000019341 magnesium sulphate Nutrition 0.000 description 7
• 150000002825 nitriles Chemical class 0.000 description 7
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 7
• 239000001301 oxygen Chemical group 0.000 description 7
• 238000002360 preparation method Methods 0.000 description 7
• 230000008569 process Effects 0.000 description 7
• 108090000765 processed proteins & peptides Proteins 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 229920006395 saturated elastomer Polymers 0.000 description 7
• 239000011593 sulfur Chemical group 0.000 description 7
• 239000006188 syrup Substances 0.000 description 7
• 235000020357 syrup Nutrition 0.000 description 7
• KNDWUKJAYRIVHS-UHFFFAOYSA-N 2-aminoadamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC1C(N)C2(C(O)=O)C3 KNDWUKJAYRIVHS-UHFFFAOYSA-N 0.000 description 6
• 102000009515 Arachidonate 15-Lipoxygenase Human genes 0.000 description 6
• 108010048907 Arachidonate 15-lipoxygenase Proteins 0.000 description 6
• XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 6
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 6
• BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 6
• 239000002552 dosage form Substances 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• 125000001188 haloalkyl group Chemical group 0.000 description 6
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 6
• 239000006186 oral dosage form Substances 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
• ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 6
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 5
• JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 5
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
• DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 5
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 229940123464 Thiazolidinedione Drugs 0.000 description 5
• 125000002252 acyl group Chemical group 0.000 description 5
• 239000000556 agonist Substances 0.000 description 5
• 229910021529 ammonia Inorganic materials 0.000 description 5
• 239000008346 aqueous phase Substances 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 229910052801 chlorine Inorganic materials 0.000 description 5
• 125000004093 cyano group Chemical group *C#N 0.000 description 5
• 125000000392 cycloalkenyl group Chemical group 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 230000002519 immonomodulatory effect Effects 0.000 description 5
• 239000012074 organic phase Substances 0.000 description 5
• 230000005195 poor health Effects 0.000 description 5
• 229910000343 potassium bisulfate Inorganic materials 0.000 description 5
• 102000004196 processed proteins & peptides Human genes 0.000 description 5
• 239000012279 sodium borohydride Substances 0.000 description 5
• 229910000033 sodium borohydride Inorganic materials 0.000 description 5
• 239000000758 substrate Substances 0.000 description 5
• 125000003396 thiol group Chemical class [H]S* 0.000 description 5
• IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 description 4
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 4
• ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 4
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 4
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
• 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 4
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
• 230000002378 acidificating effect Effects 0.000 description 4
• 150000001299 aldehydes Chemical class 0.000 description 4
• 125000005236 alkanoylamino group Chemical group 0.000 description 4
• 125000003282 alkyl amino group Chemical group 0.000 description 4
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 4
• 125000004104 aryloxy group Chemical group 0.000 description 4
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 150000001721 carbon Chemical group 0.000 description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
• 229910052802 copper Inorganic materials 0.000 description 4
• 239000010949 copper Substances 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
• 238000010511 deprotection reaction Methods 0.000 description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
• 125000004438 haloalkoxy group Chemical group 0.000 description 4
• 125000005843 halogen group Chemical group 0.000 description 4
• 239000012280 lithium aluminium hydride Substances 0.000 description 4
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 4
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 4
• 238000010791 quenching Methods 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
• HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 3
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
• LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 3
• TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 3
• 102000004146 ATP citrate synthases Human genes 0.000 description 3
• 108090000662 ATP citrate synthases Proteins 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 125000003358 C2-C20 alkenyl group Chemical group 0.000 description 3
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
• 108010011459 Exenatide Proteins 0.000 description 3
• 239000004471 Glycine Substances 0.000 description 3
• 108010000817 Leuprolide Proteins 0.000 description 3
• KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• 102100040918 Pro-glucagon Human genes 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• JIMXXGFJRDUSRO-UHFFFAOYSA-N adamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC2CC1(C(=O)O)C3 JIMXXGFJRDUSRO-UHFFFAOYSA-N 0.000 description 3
• 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 description 3
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 3
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 3
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 3
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 3
• 125000003277 amino group Chemical group 0.000 description 3
• 230000002058 anti-hyperglycaemic effect Effects 0.000 description 3
• 239000003529 anticholesteremic agent Substances 0.000 description 3
• 125000001769 aryl amino group Chemical group 0.000 description 3
• 125000005135 aryl sulfinyl group Chemical group 0.000 description 3
• 125000005110 aryl thio group Chemical group 0.000 description 3
• 239000003613 bile acid Substances 0.000 description 3
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 3
• 238000005119 centrifugation Methods 0.000 description 3
• 150000001793 charged compounds Chemical class 0.000 description 3
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 3
• 238000009833 condensation Methods 0.000 description 3
• 230000005494 condensation Effects 0.000 description 3
• WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine mesylate Natural products CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 description 3
• 238000001514 detection method Methods 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
• 229910000397 disodium phosphate Inorganic materials 0.000 description 3
• 235000019800 disodium phosphate Nutrition 0.000 description 3
• 238000010828 elution Methods 0.000 description 3
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• KZNQNBZMBZJQJO-YFKPBYRVSA-N glyclproline Chemical compound NCC(=O)N1CCC[C@H]1C(O)=O KZNQNBZMBZJQJO-YFKPBYRVSA-N 0.000 description 3
• 108010077515 glycylproline Proteins 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 150000002430 hydrocarbons Chemical group 0.000 description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
• 230000000055 hyoplipidemic effect Effects 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 210000004185 liver Anatomy 0.000 description 3
• 239000002697 lyase inhibitor Substances 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 description 3
• 239000003538 oral antidiabetic agent Substances 0.000 description 3
• 239000012044 organic layer Substances 0.000 description 3
• 239000012285 osmium tetroxide Substances 0.000 description 3
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 3
• 229910052763 palladium Inorganic materials 0.000 description 3
• 238000005897 peptide coupling reaction Methods 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 238000002953 preparative HPLC Methods 0.000 description 3
• 238000000039 preparative column chromatography Methods 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 238000006722 reduction reaction Methods 0.000 description 3
• 230000002441 reversible effect Effects 0.000 description 3
• RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 3
• 230000028327 secretion Effects 0.000 description 3
• 229910000104 sodium hydride Inorganic materials 0.000 description 3
• 239000001488 sodium phosphate Substances 0.000 description 3
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
• 238000005406 washing Methods 0.000 description 3
• QJCNLJWUIOIMMF-YUMQZZPRSA-N (2s,3s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C QJCNLJWUIOIMMF-YUMQZZPRSA-N 0.000 description 2
• MDVGOOIANLZFCP-UHFFFAOYSA-N 1-adamantylmethanol Chemical compound C1C(C2)CC3CC2CC1(CO)C3 MDVGOOIANLZFCP-UHFFFAOYSA-N 0.000 description 2
• YWWWGFSJHCFVOW-QMMMGPOBSA-N 1-o-tert-butyl 2-o-ethyl (2s)-5-oxopyrrolidine-1,2-dicarboxylate Chemical compound CCOC(=O)[C@@H]1CCC(=O)N1C(=O)OC(C)(C)C YWWWGFSJHCFVOW-QMMMGPOBSA-N 0.000 description 2
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 2
• PYTMYKVIJXPNBD-OQKDUQJOSA-N 2-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylethanamine;hydron;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 PYTMYKVIJXPNBD-OQKDUQJOSA-N 0.000 description 2
• XRSAGGHWUAXBPG-UHFFFAOYSA-N 2-amino-2-hydroxyadamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC1C(N)(O)C2(C(O)=O)C3 XRSAGGHWUAXBPG-UHFFFAOYSA-N 0.000 description 2
• CZMRCDWAGMRECN-UHFFFAOYSA-N 2-{[3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OCC1OC(CO)(OC2OC(CO)C(O)C(O)C2O)C(O)C1O CZMRCDWAGMRECN-UHFFFAOYSA-N 0.000 description 2
• LRFZIPCTFBPFLX-UHFFFAOYSA-N 3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)C(C)(C)C LRFZIPCTFBPFLX-UHFFFAOYSA-N 0.000 description 2
• MVDXXGIBARMXSA-PYUWXLGESA-N 5-[[(2r)-2-benzyl-3,4-dihydro-2h-chromen-6-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC1=CC=C(O[C@@H](CC=2C=CC=CC=2)CC2)C2=C1 MVDXXGIBARMXSA-PYUWXLGESA-N 0.000 description 2
• OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 2
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• 125000003860 C1-C20 alkoxy group Chemical group 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 description 2
• 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 description 2
• 241000699800 Cricetinae Species 0.000 description 2
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
• 108010036949 Cyclosporine Proteins 0.000 description 2
• BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 2
• 102000051325 Glucagon Human genes 0.000 description 2
• 108060003199 Glucagon Proteins 0.000 description 2
• 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 2
• 229910004373 HOAc Inorganic materials 0.000 description 2
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
• 101710092928 Insulin-like peptide-1 Proteins 0.000 description 2
• 102000004895 Lipoproteins Human genes 0.000 description 2
• 108090001030 Lipoproteins Proteins 0.000 description 2
• AHLBNYSZXLDEJQ-UHFFFAOYSA-N N-formyl-L-leucylester Natural products CCCCCCCCCCCC(OC(=O)C(CC(C)C)NC=O)CC1OC(=O)C1CCCCCC AHLBNYSZXLDEJQ-UHFFFAOYSA-N 0.000 description 2
• 238000005481 NMR spectroscopy Methods 0.000 description 2
• BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
• 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 2
• XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 2
• 238000007059 Strecker synthesis reaction Methods 0.000 description 2
• DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 description 2
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
• WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 2
• ATZKAUGGNMSCCY-VVFNRDJMSA-N [(1r,2r,3r)-2-[(3e)-4,8-dimethylnona-3,7-dienyl]-2-methyl-3-[(1e,5e)-2,6,10-trimethylundeca-1,5,9-trienyl]cyclopropyl]methyl phosphono hydrogen phosphate Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\[C@@H]1[C@@H](COP(O)(=O)OP(O)(O)=O)[C@]1(C)CC\C=C(/C)CCC=C(C)C ATZKAUGGNMSCCY-VVFNRDJMSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 229960001138 acetylsalicylic acid Drugs 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• DZULQZKFBAHSRX-UHFFFAOYSA-N adamantane-1-carbaldehyde Chemical compound C1C(C2)CC3CC2CC1(C=O)C3 DZULQZKFBAHSRX-UHFFFAOYSA-N 0.000 description 2
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
• 125000004450 alkenylene group Chemical group 0.000 description 2
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 2
• 125000002947 alkylene group Chemical group 0.000 description 2
• 125000005095 alkynylaminocarbonyl group Chemical group 0.000 description 2
• 125000001091 aminosulfinyl group Chemical group [H]N([H])S(*)=O 0.000 description 2
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 2
• BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
• 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
• 235000011130 ammonium sulphate Nutrition 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 230000000879 anti-atherosclerotic effect Effects 0.000 description 2
• 230000003078 antioxidant effect Effects 0.000 description 2
• 239000012223 aqueous fraction Substances 0.000 description 2
• 125000004659 aryl alkyl thio group Chemical group 0.000 description 2
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
• 125000005160 aryl oxy alkyl group Chemical group 0.000 description 2
• 125000005162 aryl oxy carbonyl amino group Chemical group 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 229960002170 azathioprine Drugs 0.000 description 2
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
• PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 2
• 150000001576 beta-amino acids Chemical class 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 239000006227 byproduct Substances 0.000 description 2
• 125000001589 carboacyl group Chemical group 0.000 description 2
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
• 229940047495 celebrex Drugs 0.000 description 2
• JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 2
• SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 2
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
• 238000005888 cyclopropanation reaction Methods 0.000 description 2
• QQKNSPHAFATFNQ-UHFFFAOYSA-N darglitazone Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCC(=O)C(C=C1)=CC=C1CC1SC(=O)NC1=O QQKNSPHAFATFNQ-UHFFFAOYSA-N 0.000 description 2
• 230000018044 dehydration Effects 0.000 description 2
• 238000006297 dehydration reaction Methods 0.000 description 2
• CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 125000004663 dialkyl amino group Chemical group 0.000 description 2
• 229960002656 didanosine Drugs 0.000 description 2
• 235000005911 diet Nutrition 0.000 description 2
• 230000037213 diet Effects 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 208000035475 disorder Diseases 0.000 description 2
• 229940125542 dual agonist Drugs 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• TXXWSOKUXUMWRZ-UHFFFAOYSA-N ethyl 2-cyclopentylideneacetate Chemical compound CCOC(=O)C=C1CCCC1 TXXWSOKUXUMWRZ-UHFFFAOYSA-N 0.000 description 2
• 239000002024 ethyl acetate extract Substances 0.000 description 2
• 229960001519 exenatide Drugs 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 238000004108 freeze drying Methods 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 2
• 229960004666 glucagon Drugs 0.000 description 2
• 239000003862 glucocorticoid Substances 0.000 description 2
• XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 2
• 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 2
• 230000002440 hepatic effect Effects 0.000 description 2
• 125000004447 heteroarylalkenyl group Chemical group 0.000 description 2
• 125000005241 heteroarylamino group Chemical group 0.000 description 2
• 125000005553 heteroaryloxy group Chemical group 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 125000005350 hydroxycycloalkyl group Chemical group 0.000 description 2
• 230000000871 hypocholesterolemic effect Effects 0.000 description 2
• 229960001680 ibuprofen Drugs 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 2
• JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 2
• RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 description 2
• 125000005647 linker group Chemical group 0.000 description 2
• 230000037356 lipid metabolism Effects 0.000 description 2
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
• 238000011068 loading method Methods 0.000 description 2
• 229940087857 lupron Drugs 0.000 description 2
• 206010025135 lupus erythematosus Diseases 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
• 230000014759 maintenance of location Effects 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 2
• CLYOOVNORYNXMD-UHFFFAOYSA-N methyl adamantane-1-carboxylate Chemical compound C1C(C2)CC3CC2CC1(C(=O)OC)C3 CLYOOVNORYNXMD-UHFFFAOYSA-N 0.000 description 2
• 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
• 235000019796 monopotassium phosphate Nutrition 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 2
• QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 2
• 229960003512 nicotinic acid Drugs 0.000 description 2
• 235000001968 nicotinic acid Nutrition 0.000 description 2
• 239000011664 nicotinic acid Substances 0.000 description 2
• 238000002414 normal-phase solid-phase extraction Methods 0.000 description 2
• 238000007248 oxidative elimination reaction Methods 0.000 description 2
• 125000004043 oxo group Chemical group O=* 0.000 description 2
• 229940000596 parlodel Drugs 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 2
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 2
• 125000006684 polyhaloalkyl group Polymers 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 229960003912 probucol Drugs 0.000 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 description 2
• 238000012545 processing Methods 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 2
• QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 239000000849 selective androgen receptor modulator Substances 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
• 239000002594 sorbent Substances 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 229940037128 systemic glucocorticoids Drugs 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
• CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
• 150000003672 ureas Chemical class 0.000 description 2
• 208000019553 vascular disease Diseases 0.000 description 2
• 229940087652 vioxx Drugs 0.000 description 2
• 239000003039 volatile agent Substances 0.000 description 2
• 238000010792 warming Methods 0.000 description 2
• 229960000523 zalcitabine Drugs 0.000 description 2
• HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 2
• 239000011701 zinc Substances 0.000 description 2
• 239000011592 zinc chloride Substances 0.000 description 2
• 235000005074 zinc chloride Nutrition 0.000 description 2
• LRFZIPCTFBPFLX-SSDOTTSWSA-N (2s)-3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)C(C)(C)C LRFZIPCTFBPFLX-SSDOTTSWSA-N 0.000 description 1
• MCEWPPMUTVLMJG-YCXLAJEKSA-N (3s)-2-azabicyclo[3.1.0]hexane-3-carboxamide Chemical compound N1[C@H](C(=O)N)CC2CC21 MCEWPPMUTVLMJG-YCXLAJEKSA-N 0.000 description 1
• RWIUTHWKQHRQNP-ZDVGBALWSA-N (9e,12e)-n-(1-phenylethyl)octadeca-9,12-dienamide Chemical compound CCCCC\C=C\C\C=C\CCCCCCCC(=O)NC(C)C1=CC=CC=C1 RWIUTHWKQHRQNP-ZDVGBALWSA-N 0.000 description 1
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
• JLHMJWHSBYZWJJ-UHFFFAOYSA-N 1,2-thiazole 1-oxide Chemical class O=S1C=CC=N1 JLHMJWHSBYZWJJ-UHFFFAOYSA-N 0.000 description 1
• NUBQKPWHXMGDLP-UHFFFAOYSA-N 1-[4-benzyl-2-hydroxy-5-[(2-hydroxy-2,3-dihydro-1h-inden-1-yl)amino]-5-oxopentyl]-n-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide;sulfuric acid Chemical compound OS(O)(=O)=O.C1CN(CC(O)CC(CC=2C=CC=CC=2)C(=O)NC2C3=CC=CC=C3CC2O)C(C(=O)NC(C)(C)C)CN1CC1=CC=CN=C1 NUBQKPWHXMGDLP-UHFFFAOYSA-N 0.000 description 1
• JGGVUBCVOSWFHN-UHFFFAOYSA-N 1-cyclopentylideneethanol Chemical compound CC(O)=C1CCCC1 JGGVUBCVOSWFHN-UHFFFAOYSA-N 0.000 description 1
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
• PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
• KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical group C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 1
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
• 229940123153 15 Lipoxygenase inhibitor Drugs 0.000 description 1
• OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 1
• GZJZZQHTBTUBEL-HNNXBMFYSA-N 2-[4-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]ethoxy]phenyl]acetic acid Chemical compound C1=NC(N)=CC=C1[C@@H](O)CNCCOC1=CC=C(CC(O)=O)C=C1 GZJZZQHTBTUBEL-HNNXBMFYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• 125000006040 2-hexenyl group Chemical group 0.000 description 1
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
• DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical compound NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• CFLAHQSWDKNWPW-UHFFFAOYSA-N 3-(benzyloxy)-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)OCC1=CC=CC=C1 CFLAHQSWDKNWPW-UHFFFAOYSA-N 0.000 description 1
• NBYATBIMYLFITE-UHFFFAOYSA-N 3-[decyl(dimethyl)silyl]-n-[2-(4-methylphenyl)-1-phenylethyl]propanamide Chemical compound C=1C=CC=CC=1C(NC(=O)CC[Si](C)(C)CCCCCCCCCC)CC1=CC=C(C)C=C1 NBYATBIMYLFITE-UHFFFAOYSA-N 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
• 125000006041 3-hexenyl group Chemical group 0.000 description 1
• LHCOVOKZWQYODM-CPEOKENHSA-N 4-amino-1-[(2r,5s)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one;1-[(2r,4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1.O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 LHCOVOKZWQYODM-CPEOKENHSA-N 0.000 description 1
• FUSNOPLQVRUIIM-UHFFFAOYSA-N 4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-n-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide Chemical compound O=C1NC(C)(C)CN1C(N=C1N)=NC=C1C(=O)NC1=CC=CC(C(F)(F)F)=C1 FUSNOPLQVRUIIM-UHFFFAOYSA-N 0.000 description 1
• MXNQOXJLUJUCGE-UHFFFAOYSA-N 4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-n-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide;hydrochloride Chemical compound Cl.O=C1NC(C)(C)CN1C(N=C1N)=NC=C1C(=O)NC1=CC=CC(C(F)(F)F)=C1 MXNQOXJLUJUCGE-UHFFFAOYSA-N 0.000 description 1
• WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
• NFFXEUUOMTXWCX-UHFFFAOYSA-N 5-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]-2-methoxy-n-[[4-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C(F)(F)F)C(OC)=CC=C1CC1SC(=O)NC1=O NFFXEUUOMTXWCX-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-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
• ZCLFPKBADABTMG-UHFFFAOYSA-N 9-[4-[4-[[2-(2,2,2-trifluoroethoxy)benzoyl]amino]piperidin-1-yl]butyl]-n-(2,2,2-trifluoroethyl)fluorene-9-carboxamide Chemical group C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN(CC1)CCC1NC(=O)C1=CC=CC=C1OCC(F)(F)F ZCLFPKBADABTMG-UHFFFAOYSA-N 0.000 description 1
• DJQOOSBJCLSSEY-UHFFFAOYSA-N Acipimox Chemical compound CC1=CN=C(C(O)=O)C=[N+]1[O-] DJQOOSBJCLSSEY-UHFFFAOYSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 102100033367 Appetite-regulating hormone Human genes 0.000 description 1
• 101710111255 Appetite-regulating hormone Proteins 0.000 description 1
• 102100024881 C3 and PZP-like alpha-2-macroglobulin domain-containing protein 8 Human genes 0.000 description 1
• QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 229940122502 Cholesterol absorption inhibitor Drugs 0.000 description 1
• 229920001268 Cholestyramine Polymers 0.000 description 1
• KPSRODZRAIWAKH-JTQLQIEISA-N Ciprofibrate Natural products C1=CC(OC(C)(C)C(O)=O)=CC=C1[C@H]1C(Cl)(Cl)C1 KPSRODZRAIWAKH-JTQLQIEISA-N 0.000 description 1
• 238000005821 Claisen rearrangement reaction Methods 0.000 description 1
• BMOVQUBVGICXQN-UHFFFAOYSA-N Clinofibrate Chemical compound C1=CC(OC(C)(CC)C(O)=O)=CC=C1C1(C=2C=CC(OC(C)(CC)C(O)=O)=CC=2)CCCCC1 BMOVQUBVGICXQN-UHFFFAOYSA-N 0.000 description 1
• 229920002911 Colestipol Polymers 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
• 102000034534 Cotransporters Human genes 0.000 description 1
• 108020003264 Cotransporters Proteins 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
• 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
• XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• 229930105110 Cyclosporin A Natural products 0.000 description 1
• 206010011831 Cytomegalovirus infection Diseases 0.000 description 1
• HPJYKMSFRBJOSW-JHSUYXJUSA-N Damsin Chemical compound C[C@H]1CC[C@H]2C(=C)C(=O)O[C@H]2[C@]2(C)C(=O)CC[C@@H]12 HPJYKMSFRBJOSW-JHSUYXJUSA-N 0.000 description 1
• 241000350052 Daniellia ogea Species 0.000 description 1
• 108010016626 Dipeptides Proteins 0.000 description 1
• SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
• CYQFCXCEBYINGO-DLBZAZTESA-N Dronabinol Natural products C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@H]21 CYQFCXCEBYINGO-DLBZAZTESA-N 0.000 description 1
• DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 1
• HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 1
• 102400000326 Glucagon-like peptide 2 Human genes 0.000 description 1
• 101800000221 Glucagon-like peptide 2 Proteins 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
• 108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
• 108010051696 Growth Hormone Proteins 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 229940122199 Insulin secretagogue Drugs 0.000 description 1
• 206010067745 Intestinal mucosal atrophy Diseases 0.000 description 1
• 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
• 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 1
• UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
• 238000006000 Knoevenagel condensation reaction Methods 0.000 description 1
• 150000008575 L-amino acids Chemical class 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• 102000007330 LDL Lipoproteins Human genes 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 239000002841 Lewis acid Substances 0.000 description 1
• 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 229940122014 Lyase inhibitor Drugs 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 101710151321 Melanostatin Proteins 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 238000006845 Michael addition reaction Methods 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 241000872931 Myoporum sandwicense Species 0.000 description 1
• 150000001204 N-oxides Chemical class 0.000 description 1
• 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
• CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
• 229930193140 Neomycin Natural products 0.000 description 1
• 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 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
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 102100028427 Pro-neuropeptide Y Human genes 0.000 description 1
• 102000035554 Proglucagon Human genes 0.000 description 1
• 108010058003 Proglucagon Proteins 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
• AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 229920005654 Sephadex Polymers 0.000 description 1
• 239000012507 Sephadex™ Substances 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• 102100022831 Somatoliberin Human genes 0.000 description 1
• 101710142969 Somatoliberin Proteins 0.000 description 1
• 102100038803 Somatotropin Human genes 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 102000003673 Symporters Human genes 0.000 description 1
• 108090000088 Symporters Proteins 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 1
• XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• GLWHPRRGGYLLRV-XLPZGREQSA-N [[(2s,3s,5r)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](N=[N+]=[N-])C1 GLWHPRRGGYLLRV-XLPZGREQSA-N 0.000 description 1
• 210000000683 abdominal cavity Anatomy 0.000 description 1
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
• DFDGRKNOFOJBAJ-UHFFFAOYSA-N acifran Chemical compound C=1C=CC=CC=1C1(C)OC(C(O)=O)=CC1=O DFDGRKNOFOJBAJ-UHFFFAOYSA-N 0.000 description 1
• 229950000146 acifran Drugs 0.000 description 1
• 229960003526 acipimox Drugs 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 229960004343 alendronic acid Drugs 0.000 description 1
• 229910001413 alkali metal ion Inorganic materials 0.000 description 1
• 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 125000005089 alkenylaminocarbonyl group Chemical group 0.000 description 1
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
• 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 description 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
• 125000004419 alkynylene group Chemical group 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 229960004909 aminosalicylic acid Drugs 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
• 230000002924 anti-infective effect Effects 0.000 description 1
• 229940127226 anticholesterol agent Drugs 0.000 description 1
• 229940058303 antinematodal benzimidazole derivative Drugs 0.000 description 1
• 125000003435 aroyl group Chemical group 0.000 description 1
• 125000005018 aryl alkenyl group Chemical group 0.000 description 1
• 125000001691 aryl alkyl amino group Chemical group 0.000 description 1
• 125000005100 aryl amino carbonyl group Chemical group 0.000 description 1
• 125000005129 aryl carbonyl group Chemical group 0.000 description 1
• 125000005199 aryl carbonyloxy group Chemical group 0.000 description 1
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
• 125000005164 aryl thioalkyl group Chemical group 0.000 description 1
• 125000005325 aryloxy aryl group Chemical group 0.000 description 1
• 229940072224 asacol Drugs 0.000 description 1
• 238000010533 azeotropic distillation Methods 0.000 description 1
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 229960000516 bezafibrate Drugs 0.000 description 1
• IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
• 150000004283 biguanides Chemical class 0.000 description 1
• 229920000080 bile acid sequestrant Polymers 0.000 description 1
• 229940096699 bile acid sequestrants Drugs 0.000 description 1
• 230000002051 biphasic effect Effects 0.000 description 1
• 239000012455 biphasic mixture Substances 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
• 229960002802 bromocriptine Drugs 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 235000013877 carbamide Nutrition 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 125000005392 carboxamide group Chemical group NC(=O)* 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 238000010531 catalytic reduction reaction Methods 0.000 description 1
• 229960000590 celecoxib Drugs 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• MVCQKIKWYUURMU-UHFFFAOYSA-N cetilistat Chemical compound C1=C(C)C=C2C(=O)OC(OCCCCCCCCCCCCCCCC)=NC2=C1 MVCQKIKWYUURMU-UHFFFAOYSA-N 0.000 description 1
• 229950002397 cetilistat Drugs 0.000 description 1
• KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 230000001906 cholesterol absorption Effects 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 229960001265 ciclosporin Drugs 0.000 description 1
• 229960002174 ciprofibrate Drugs 0.000 description 1
• KPSRODZRAIWAKH-UHFFFAOYSA-N ciprofibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C(Cl)(Cl)C1 KPSRODZRAIWAKH-UHFFFAOYSA-N 0.000 description 1
• 229950003072 clinofibrate Drugs 0.000 description 1
• 229960002604 colestipol Drugs 0.000 description 1
• GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
• 229940014461 combivir Drugs 0.000 description 1
• 230000000052 comparative effect Effects 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 230000000536 complexating effect Effects 0.000 description 1
• 238000010924 continuous production Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000013256 coordination polymer Substances 0.000 description 1
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
• 229940111134 coxibs Drugs 0.000 description 1
• 229940088900 crixivan Drugs 0.000 description 1
• 229940045803 cuprous chloride Drugs 0.000 description 1
• 125000005112 cycloalkylalkoxy group Chemical group 0.000 description 1
• 125000002993 cycloalkylene group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 150000001942 cyclopropanes Chemical class 0.000 description 1
• 229930182912 cyclosporin Natural products 0.000 description 1
• POZRVZJJTULAOH-LHZXLZLDSA-N danazol Chemical compound C1[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=CC2=C1C=NO2 POZRVZJJTULAOH-LHZXLZLDSA-N 0.000 description 1
• 229960000766 danazol Drugs 0.000 description 1
• 229950006689 darglitazone Drugs 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 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 1
• 230000000593 degrading effect Effects 0.000 description 1
• 229960000475 delavirdine mesylate Drugs 0.000 description 1
• MEPNHSOMXMALDZ-UHFFFAOYSA-N delavirdine mesylate Chemical compound CS(O)(=O)=O.CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 MEPNHSOMXMALDZ-UHFFFAOYSA-N 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 239000002037 dichloromethane fraction Substances 0.000 description 1
• 229960001193 diclofenac sodium Drugs 0.000 description 1
• 150000005690 diesters Chemical class 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 229940043279 diisopropylamine Drugs 0.000 description 1
• HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 125000003438 dodecyl 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])C([H])([H])C([H])([H])* 0.000 description 1
• 229960004242 dronabinol Drugs 0.000 description 1
• 229950002375 englitazone Drugs 0.000 description 1
• 229940072253 epivir Drugs 0.000 description 1
• QYJOOVQLTTVTJY-YFKPBYRVSA-N ethyl (2s)-5-oxopyrrolidine-2-carboxylate Chemical compound CCOC(=O)[C@@H]1CCC(=O)N1 QYJOOVQLTTVTJY-YFKPBYRVSA-N 0.000 description 1
• WHQLQYRFIHPMNA-UHFFFAOYSA-N ethyl acetate;oxolane Chemical compound C1CCOC1.CCOC(C)=O WHQLQYRFIHPMNA-UHFFFAOYSA-N 0.000 description 1
• 229960003750 ethyl chloride Drugs 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• 229940083571 etidronate disodium Drugs 0.000 description 1
• GWBBVOVXJZATQQ-UHFFFAOYSA-L etidronate disodium Chemical compound [Na+].[Na+].OP(=O)([O-])C(O)(C)P(O)([O-])=O GWBBVOVXJZATQQ-UHFFFAOYSA-L 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 229940085363 evista Drugs 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 229940065410 feldene Drugs 0.000 description 1
• 239000002871 fertility agent Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 229940001490 fosamax Drugs 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 230000030136 gastric emptying Effects 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 238000002523 gelfiltration Methods 0.000 description 1
• 229960004346 glimepiride Drugs 0.000 description 1
• WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
• 108010063245 glucagon-like peptide 1 (7-36)amide Proteins 0.000 description 1
• TWSALRJGPBVBQU-PKQQPRCHSA-N glucagon-like peptide 2 Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O)[C@@H](C)CC)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=CC=C1 TWSALRJGPBVBQU-PKQQPRCHSA-N 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 230000013595 glycosylation Effects 0.000 description 1
• 238000006206 glycosylation reaction Methods 0.000 description 1
• XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical class C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 150000004795 grignard reagents Chemical class 0.000 description 1
• 239000000122 growth hormone Substances 0.000 description 1
• 239000003324 growth hormone secretagogue Substances 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 230000023597 hemostasis Effects 0.000 description 1
• 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 1
• 125000005114 heteroarylalkoxy group Chemical group 0.000 description 1
• 125000005368 heteroarylthio group Chemical group 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 238000007327 hydrogenolysis reaction Methods 0.000 description 1
• MSYBLBLAMDYKKZ-UHFFFAOYSA-N hydron;pyridine-3-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=CN=C1 MSYBLBLAMDYKKZ-UHFFFAOYSA-N 0.000 description 1
• XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 1
• 229960004171 hydroxychloroquine Drugs 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 229950010293 imanixil Drugs 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• NUBQKPWHXMGDLP-BDEHJDMKSA-N indinavir sulfate Chemical compound OS(O)(=O)=O.C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 NUBQKPWHXMGDLP-BDEHJDMKSA-N 0.000 description 1
• 229960004243 indinavir sulfate Drugs 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 229960000905 indomethacin Drugs 0.000 description 1
• 229940125699 infertility agent Drugs 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 230000003914 insulin secretion Effects 0.000 description 1
• 239000013067 intermediate product Substances 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 229940088976 invirase Drugs 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 229960004384 ketorolac tromethamine Drugs 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229960001627 lamivudine Drugs 0.000 description 1
• 229940033984 lamivudine / zidovudine Drugs 0.000 description 1
• GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
• 229960004338 leuprorelin Drugs 0.000 description 1
• 150000007517 lewis acids Chemical class 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 229910001416 lithium ion Inorganic materials 0.000 description 1
• OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
• 150000002690 malonic acid derivatives Chemical class 0.000 description 1
• 229940099262 marinol Drugs 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• 229940090004 megace Drugs 0.000 description 1
• 229960004296 megestrol acetate Drugs 0.000 description 1
• 229950008446 melinamide Drugs 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 229960004963 mesalazine Drugs 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• 229960004329 metformin hydrochloride Drugs 0.000 description 1
• OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• HOVAGTYPODGVJG-VEIUFWFVSA-N methyl alpha-D-mannoside Chemical compound CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O HOVAGTYPODGVJG-VEIUFWFVSA-N 0.000 description 1
• AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 1
• 229950009116 mevastatin Drugs 0.000 description 1
• BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
• WGESLFUSXZBFQF-UHFFFAOYSA-N n-methyl-n-prop-2-enylprop-2-en-1-amine Chemical compound C=CCN(C)CC=C WGESLFUSXZBFQF-UHFFFAOYSA-N 0.000 description 1
• 229960004270 nabumetone Drugs 0.000 description 1
• 229960002009 naproxen Drugs 0.000 description 1
• CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
• 208000037931 necrotizing enteritis Diseases 0.000 description 1
• 229960000884 nelfinavir Drugs 0.000 description 1
• 229960004927 neomycin Drugs 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
• 125000002560 nitrile group Chemical group 0.000 description 1
• 230000006959 non-competitive inhibition Effects 0.000 description 1
• 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 230000036963 noncompetitive effect Effects 0.000 description 1
• 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 1
• 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 1
• 229940072250 norvir Drugs 0.000 description 1
• 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 1
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
• 229940127234 oral contraceptive Drugs 0.000 description 1
• 239000003539 oral contraceptive agent Substances 0.000 description 1
• 125000000962 organic group Chemical group 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 238000005949 ozonolysis reaction Methods 0.000 description 1
• 230000020477 pH reduction Effects 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• 210000002824 peroxisome Anatomy 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
• 229960003243 phenformin Drugs 0.000 description 1
• 230000008288 physiological mechanism Effects 0.000 description 1
• 229960002702 piroxicam Drugs 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
• 229920000371 poly(diallyldimethylammonium chloride) polymer Polymers 0.000 description 1
• 239000004810 polytetrafluoroethylene Substances 0.000 description 1
• 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
• 230000001323 posttranslational effect Effects 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 235000010259 potassium hydrogen sulphite Nutrition 0.000 description 1
• 239000012286 potassium permanganate Substances 0.000 description 1
• LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
• 150000003858 primary carboxamides Chemical group 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 239000000583 progesterone congener Substances 0.000 description 1
• 229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 230000000644 propagated effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 230000000541 pulsatile effect Effects 0.000 description 1
• 229960004622 raloxifene Drugs 0.000 description 1
• 230000009103 reabsorption Effects 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 229940087462 relafen Drugs 0.000 description 1
• 229940063627 rescriptor Drugs 0.000 description 1
• 229940064914 retrovir Drugs 0.000 description 1
• 229960000311 ritonavir Drugs 0.000 description 1
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
• 229960000371 rofecoxib Drugs 0.000 description 1
• 150000003873 salicylate salts Chemical class 0.000 description 1
• 229940063122 sandimmune Drugs 0.000 description 1
• 229960001852 saquinavir Drugs 0.000 description 1
• 230000036186 satiety Effects 0.000 description 1
• 235000019627 satiety Nutrition 0.000 description 1
• IMNTVVOUWFPRSB-JWQCQUIFSA-N sch-48461 Chemical compound C1=CC(OC)=CC=C1[C@H]1N(C=2C=CC(OC)=CC=2)C(=O)[C@@H]1CCCC1=CC=CC=C1 IMNTVVOUWFPRSB-JWQCQUIFSA-N 0.000 description 1
• 230000001235 sensitizing effect Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000003352 sequestering agent Substances 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• 229940112726 skelid Drugs 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
• GRONZTPUWOOUFQ-UHFFFAOYSA-M sodium;methanol;hydroxide Chemical compound [OH-].[Na+].OC GRONZTPUWOOUFQ-UHFFFAOYSA-M 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 229960001203 stavudine Drugs 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
• NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
• 229960001940 sulfasalazine Drugs 0.000 description 1
• NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• CPDDZSSEAVLMRY-FEQFWAPWSA-N tegaserod maleate Chemical compound [H+].[H+].[O-]C(=O)\C=C/C([O-])=O.C1=C(OC)C=C2C(/C=N/NC(=N)NCCCCC)=CNC2=C1 CPDDZSSEAVLMRY-FEQFWAPWSA-N 0.000 description 1
• 150000003505 terpenes Chemical class 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 150000001467 thiazolidinediones Chemical class 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 125000004001 thioalkyl group Chemical group 0.000 description 1
• 229940019375 tiludronate Drugs 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
• 229960002044 tolmetin sodium Drugs 0.000 description 1
• QGUALMNFRILWRA-UHFFFAOYSA-M tolmetin sodium Chemical compound [Na+].C1=CC(C)=CC=C1C(=O)C1=CC=C(CC([O-])=O)N1C QGUALMNFRILWRA-UHFFFAOYSA-M 0.000 description 1
• 229940019127 toradol Drugs 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 125000004385 trihaloalkyl group Chemical group 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 125000002948 undecyl 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])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000003828 vacuum filtration Methods 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 229940023080 viracept Drugs 0.000 description 1
• 230000003313 weakening effect Effects 0.000 description 1
• 229940087450 zerit Drugs 0.000 description 1
• 229960002555 zidovudine Drugs 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1