JP5134974B2 - 血漿中のグルコースレベル、コレステロールレベル及びトリグリセリドレベルを低下させるための５−［４−（４−（２−アミノ−２−メトキシカルボニルエチル）フェノキシ）ベンジリデン］チアゾリジン−２，４−ジオン誘導体及び関連化合物 - Google Patents
血漿中のグルコースレベル、コレステロールレベル及びトリグリセリドレベルを低下させるための５−［４−（４−（２−アミノ−２−メトキシカルボニルエチル）フェノキシ）ベンジリデン］チアゾリジン−２，４−ジオン誘導体及び関連化合物 Download PDFInfo
- Publication number
- JP5134974B2 JP5134974B2 JP2007556366A JP2007556366A JP5134974B2 JP 5134974 B2 JP5134974 B2 JP 5134974B2 JP 2007556366 A JP2007556366 A JP 2007556366A JP 2007556366 A JP2007556366 A JP 2007556366A JP 5134974 B2 JP5134974 B2 JP 5134974B2
- Authority
- JP
- Japan
- Prior art keywords
- phenoxy
- amino
- phenyl
- thiazolidine
- ylmethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 title claims description 95
- -1 2- (Amino-2-methoxycarbonylethyl) phenoxy Chemical group 0.000 title claims description 33
- 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 title claims description 29
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 title claims description 29
- 239000008103 glucose Substances 0.000 title claims description 29
- 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 title claims description 22
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 title claims description 20
- 235000012000 cholesterol Nutrition 0.000 title claims description 4
- 150000001473 2,4-thiazolidinediones Chemical class 0.000 title 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 title 1
- 238000011282 treatment Methods 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 25
- 206010012601 diabetes mellitus Diseases 0.000 claims description 21
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 14
- 206010022489 Insulin Resistance Diseases 0.000 claims description 11
- USGKBRMYSUMVLX-KHTASDDNSA-N methyl (2s)-2-amino-3-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]propanoate;hydrochloride Chemical group Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 USGKBRMYSUMVLX-KHTASDDNSA-N 0.000 claims description 11
- VLZHHJDUFBVTSS-VPVGQWTESA-N (2s)-2-amino-3-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]propanoic acid;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(O)=O)=CC=C1OC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 VLZHHJDUFBVTSS-VPVGQWTESA-N 0.000 claims description 10
- 208000008589 Obesity Diseases 0.000 claims description 8
- 235000020824 obesity Nutrition 0.000 claims description 8
- 150000003626 triacylglycerols Chemical class 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000017442 Retinal disease Diseases 0.000 claims description 3
- 206010038923 Retinopathy Diseases 0.000 claims description 3
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 3
- 229930195729 fatty acid Natural products 0.000 claims description 3
- 239000000194 fatty acid Substances 0.000 claims description 3
- 150000004665 fatty acids Chemical class 0.000 claims description 3
- 235000021588 free fatty acids Nutrition 0.000 claims description 3
- 208000017169 kidney disease Diseases 0.000 claims description 3
- 201000001119 neuropathy Diseases 0.000 claims description 3
- 230000007823 neuropathy Effects 0.000 claims description 3
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 3
- 230000036470 plasma concentration Effects 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 description 39
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 36
- 229940125782 compound 2 Drugs 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 25
- 210000004369 blood Anatomy 0.000 description 25
- 239000008280 blood Substances 0.000 description 25
- 150000003839 salts Chemical class 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 102000004877 Insulin Human genes 0.000 description 18
- 108090001061 Insulin Proteins 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 229940125396 insulin Drugs 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 125000003118 aryl group Chemical group 0.000 description 17
- 238000000034 method Methods 0.000 description 16
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 14
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 14
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 14
- 125000000217 alkyl group Chemical group 0.000 description 14
- 229940125878 compound 36 Drugs 0.000 description 14
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 13
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 13
- 229940126142 compound 16 Drugs 0.000 description 13
- 230000004054 inflammatory process Effects 0.000 description 13
- 206010061218 Inflammation Diseases 0.000 description 12
- 125000003545 alkoxy group Chemical group 0.000 description 12
- 230000037396 body weight Effects 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 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 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- 239000012453 solvate Substances 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 10
- 125000003342 alkenyl group Chemical group 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 208000026278 immune system disease Diseases 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 7
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 7
- 230000036772 blood pressure Effects 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 229940125810 compound 20 Drugs 0.000 description 7
- 125000005843 halogen group Chemical group 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 7
- 229960001052 streptozocin Drugs 0.000 description 7
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 6
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 108010016731 PPAR gamma Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical class C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 208000027866 inflammatory disease Diseases 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 description 5
- 102000016912 Aldehyde Reductase Human genes 0.000 description 5
- 108010053754 Aldehyde reductase Proteins 0.000 description 5
- 208000023275 Autoimmune disease Diseases 0.000 description 5
- 108010002352 Interleukin-1 Proteins 0.000 description 5
- 102000000589 Interleukin-1 Human genes 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 238000007429 general method Methods 0.000 description 5
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- KIWUVOGUEXMXSV-UHFFFAOYSA-N rhodanine Chemical compound O=C1CSC(=S)N1 KIWUVOGUEXMXSV-UHFFFAOYSA-N 0.000 description 5
- 229960004586 rosiglitazone Drugs 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 102000000536 PPAR gamma Human genes 0.000 description 4
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 4
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 4
- 210000001789 adipocyte Anatomy 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 150000003863 ammonium salts Chemical class 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 230000004190 glucose uptake Effects 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000001632 sodium acetate Substances 0.000 description 4
- 235000017281 sodium acetate Nutrition 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 0 *C(*)Cc(cc1)ccc1Oc1ccc(C=C(C(N2)=O)SC2=O)c(*)c1* Chemical compound *C(*)Cc(cc1)ccc1Oc1ccc(C=C(C(N2)=O)SC2=O)c(*)c1* 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- QZEAVTMUIIIZFS-UHFFFAOYSA-N 2-amino-3-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]-n,n-dimethylpropanamide;hydrochloride Chemical compound Cl.C1=CC(CC(N)C(=O)N(C)C)=CC=C1OC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 QZEAVTMUIIIZFS-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 102000023984 PPAR alpha Human genes 0.000 description 3
- 108010015181 PPAR delta Proteins 0.000 description 3
- 208000018262 Peripheral vascular disease Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000011759 adipose tissue development Effects 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 125000004104 aryloxy group Chemical group 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical class C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 3
- 229960001231 choline Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 229960005095 pioglitazone Drugs 0.000 description 3
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- XSCILGDBIDKOIX-SFHVURJKSA-N (2s)-3-[4-(4-formylphenoxy)phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)=CC=C1OC1=CC=C(C=O)C=C1 XSCILGDBIDKOIX-SFHVURJKSA-N 0.000 description 2
- KZTWONRVIPPDKH-UHFFFAOYSA-N 2-(piperidin-1-yl)ethanol Chemical class OCCN1CCCCC1 KZTWONRVIPPDKH-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- ALEVVOFLWAVXPD-NTISSMGPSA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1)=CC=C1C=C1C(=O)NC(=O)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1)=CC=C1C=C1C(=O)NC(=O)S1 ALEVVOFLWAVXPD-NTISSMGPSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 208000002249 Diabetes Complications Diseases 0.000 description 2
- 206010012655 Diabetic complications Diseases 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 229940122355 Insulin sensitizer Drugs 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 2
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 238000001994 activation Methods 0.000 description 2
- 230000002293 adipogenic effect Effects 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000003302 alkenyloxy group Chemical group 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical class NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 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
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000010030 glucose lowering effect Effects 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 235000019137 high fructose diet Nutrition 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- SUAMGAFNSGDUTQ-IBGZPJMESA-N methyl (2s)-3-[4-(4-formylphenoxy)phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1OC1=CC=C(C=O)C=C1 SUAMGAFNSGDUTQ-IBGZPJMESA-N 0.000 description 2
- SARPBCXOAPTYNU-IBGZPJMESA-N methyl (2s)-3-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1OC(C=C1)=CC=C1C=C1C(=O)NC(=O)S1 SARPBCXOAPTYNU-IBGZPJMESA-N 0.000 description 2
- ALEVVOFLWAVXPD-UHFFFAOYSA-N methyl 2-amino-3-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(CC(N)C(=O)OC)=CC=C1OC(C=C1)=CC=C1C=C1C(=O)NC(=O)S1 ALEVVOFLWAVXPD-UHFFFAOYSA-N 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 229910052700 potassium Chemical class 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- JVPRRTSOSZFDPV-UHFFFAOYSA-N tert-butyl n-[1-(dimethylamino)-3-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(CC(C(=O)N(C)C)NC(=O)OC(C)(C)C)=CC=C1OC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 JVPRRTSOSZFDPV-UHFFFAOYSA-N 0.000 description 2
- 150000001467 thiazolidinediones Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- CNBUSIJNWNXLQQ-NSHDSACASA-N (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CNBUSIJNWNXLQQ-NSHDSACASA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- XGCDBGRZEKYHNV-UHFFFAOYSA-N 1,1-bis(diphenylphosphino)methane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CP(C=1C=CC=CC=1)C1=CC=CC=C1 XGCDBGRZEKYHNV-UHFFFAOYSA-N 0.000 description 1
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical class CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- GUXPLBOETGHOJV-URBRKQAFSA-N 2-[(5s)-5-[[4-[4-[(2r)-2-amino-3-methoxy-3-oxopropyl]phenoxy]phenyl]methyl]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid;hydrochloride Chemical compound Cl.C1=CC(C[C@@H](N)C(=O)OC)=CC=C1OC(C=C1)=CC=C1C[C@H]1C(=O)N(CC(O)=O)C(=S)S1 GUXPLBOETGHOJV-URBRKQAFSA-N 0.000 description 1
- GUXPLBOETGHOJV-OQICONIUSA-N 2-[5-[[4-[4-[(2s)-2-amino-3-methoxy-3-oxopropyl]phenoxy]phenyl]methyl]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1)=CC=C1CC1C(=O)N(CC(O)=O)C(=S)S1 GUXPLBOETGHOJV-OQICONIUSA-N 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- KPGXRSRHYNQIFN-UHFFFAOYSA-L 2-oxoglutarate(2-) Chemical compound [O-]C(=O)CCC(=O)C([O-])=O KPGXRSRHYNQIFN-UHFFFAOYSA-L 0.000 description 1
- BYCDADIRSHRLAO-UHFFFAOYSA-N 3-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound C1=CC(CC(NC(=O)OC(C)(C)C)C(O)=O)=CC=C1OC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 BYCDADIRSHRLAO-UHFFFAOYSA-N 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-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
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000011767 Acute-Phase Proteins Human genes 0.000 description 1
- 108010062271 Acute-Phase Proteins Proteins 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- RRTARODJBBVCRK-NTISSMGPSA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)Cl)=CC=C1C=C1C(=O)N(CC(O)=O)C(=S)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)Cl)=CC=C1C=C1C(=O)N(CC(O)=O)C(=S)S1 RRTARODJBBVCRK-NTISSMGPSA-N 0.000 description 1
- VGTHKRAAABHTLW-RSAXXLAASA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)Cl)=CC=C1C=C1C(=O)NC(=O)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)Cl)=CC=C1C=C1C(=O)NC(=O)S1 VGTHKRAAABHTLW-RSAXXLAASA-N 0.000 description 1
- JLQNMEAFHXQDDO-RSAXXLAASA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)Cl)=CC=C1C=C1C(=O)NC(=S)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)Cl)=CC=C1C=C1C(=O)NC(=S)S1 JLQNMEAFHXQDDO-RSAXXLAASA-N 0.000 description 1
- JSSSNEUWJRXUQN-NTISSMGPSA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)F)=CC=C1C=C1C(=O)N(CC(O)=O)C(=S)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)F)=CC=C1C=C1C(=O)N(CC(O)=O)C(=S)S1 JSSSNEUWJRXUQN-NTISSMGPSA-N 0.000 description 1
- PPBAQBFRMJLJCQ-RSAXXLAASA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)F)=CC=C1C=C1C(=O)NC(=S)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)F)=CC=C1C=C1C(=O)NC(=S)S1 PPBAQBFRMJLJCQ-RSAXXLAASA-N 0.000 description 1
- MQCWRJBBLASLLK-RSAXXLAASA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)OC)=CC=C1C=C1C(=O)NC(=O)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)OC)=CC=C1C=C1C(=O)NC(=O)S1 MQCWRJBBLASLLK-RSAXXLAASA-N 0.000 description 1
- KRATWGJNAPBOJK-RSAXXLAASA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)OC)=CC=C1C=C1C(=O)NC(=S)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)OC)=CC=C1C=C1C(=O)NC(=S)S1 KRATWGJNAPBOJK-RSAXXLAASA-N 0.000 description 1
- KQDVSRNCMKACDU-UQKRIMTDSA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)[N+]([O-])=O)=CC=C1C=C1C(=O)NC(=O)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)[N+]([O-])=O)=CC=C1C=C1C(=O)NC(=O)S1 KQDVSRNCMKACDU-UQKRIMTDSA-N 0.000 description 1
- AIAMYYNUGPIZDT-NTISSMGPSA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1C(F)(F)F)=CC=C1C=C1C(=O)NC(=O)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1C(F)(F)F)=CC=C1C=C1C(=O)NC(=O)S1 AIAMYYNUGPIZDT-NTISSMGPSA-N 0.000 description 1
- PFQKGOPGJHLCAO-LMOVPXPDSA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1Cl)=CC=C1C=C1C(=O)N(CC(O)=O)C(=S)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1Cl)=CC=C1C=C1C(=O)N(CC(O)=O)C(=S)S1 PFQKGOPGJHLCAO-LMOVPXPDSA-N 0.000 description 1
- BVTPOLGKUNSHNR-NTISSMGPSA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1Cl)=CC=C1C=C1C(=O)NC(=O)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1Cl)=CC=C1C=C1C(=O)NC(=O)S1 BVTPOLGKUNSHNR-NTISSMGPSA-N 0.000 description 1
- BFGIMJQVSVHRPE-NTISSMGPSA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1Cl)=CC=C1C=C1C(=O)NC(=S)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1Cl)=CC=C1C=C1C(=O)NC(=S)S1 BFGIMJQVSVHRPE-NTISSMGPSA-N 0.000 description 1
- MKSUWVXEDGTFMG-NTISSMGPSA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1F)=CC=C1C=C1C(=O)NC(=O)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1F)=CC=C1C=C1C(=O)NC(=O)S1 MKSUWVXEDGTFMG-NTISSMGPSA-N 0.000 description 1
- NWOCBZUVOFZNOK-NTISSMGPSA-N Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1F)=CC=C1C=C1C(=O)NC(=S)S1 Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1F)=CC=C1C=C1C(=O)NC(=S)S1 NWOCBZUVOFZNOK-NTISSMGPSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 108091052347 Glucose transporter family Proteins 0.000 description 1
- 102000042092 Glucose transporter family Human genes 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 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
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 206010023203 Joint destruction Diseases 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 102000015731 Peptide Hormones Human genes 0.000 description 1
- 108010038988 Peptide Hormones Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- XNKKWXCGJMQTGM-YHWDYHRMSA-L [Na+].[Na+].N[C@@H](Cc1ccc(Oc2ccc(CC3SC(=O)NC3=O)cc2)cc1)C([O-])=O.N[C@@H](Cc1ccc(Oc2ccc(CC3SC(=O)NC3=O)cc2)cc1)C([O-])=O Chemical compound [Na+].[Na+].N[C@@H](Cc1ccc(Oc2ccc(CC3SC(=O)NC3=O)cc2)cc1)C([O-])=O.N[C@@H](Cc1ccc(Oc2ccc(CC3SC(=O)NC3=O)cc2)cc1)C([O-])=O XNKKWXCGJMQTGM-YHWDYHRMSA-L 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 210000000695 crystalline len Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- LJXTYJXBORAIHX-UHFFFAOYSA-N diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1 LJXTYJXBORAIHX-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical class OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 125000005639 glycero group Chemical group 0.000 description 1
- 125000004475 heteroaralkyl group Chemical group 0.000 description 1
- 125000005553 heteroaryloxy 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
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
- 201000008980 hyperinsulinism Diseases 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000012528 insulin ELISA Methods 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000004132 lipogenesis Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- GCMRADJSYIFOBU-UHFFFAOYSA-N methanol;2-methylpropan-2-ol Chemical compound OC.CC(C)(C)O GCMRADJSYIFOBU-UHFFFAOYSA-N 0.000 description 1
- NFPKUFRNPDETBE-SJORKVTESA-N methyl (2r)-2-amino-3-[4-[4-[[(5s)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-yl]methyl]phenoxy]phenyl]propanoate Chemical compound C1=CC(C[C@@H](N)C(=O)OC)=CC=C1OC(C=C1)=CC=C1C[C@H]1C(=O)NC(=S)S1 NFPKUFRNPDETBE-SJORKVTESA-N 0.000 description 1
- KVLAYTVNOCWLBX-YOXMSGLASA-N methyl (2s)-2-amino-3-[4-[2-chloro-4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)Cl)=CC=C1CC1C(=O)NC(=O)S1 KVLAYTVNOCWLBX-YOXMSGLASA-N 0.000 description 1
- UMUPRTIRIPPXJH-YOXMSGLASA-N methyl (2s)-2-amino-3-[4-[2-chloro-4-[(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)Cl)=CC=C1CC1C(=O)NC(=S)S1 UMUPRTIRIPPXJH-YOXMSGLASA-N 0.000 description 1
- HWWJPEZCOPEMLM-YOXMSGLASA-N methyl (2s)-2-amino-3-[4-[2-fluoro-4-[(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)F)=CC=C1CC1C(=O)NC(=S)S1 HWWJPEZCOPEMLM-YOXMSGLASA-N 0.000 description 1
- ZUWYXYIQUCLKTP-PDFNFFLASA-N methyl (2s)-2-amino-3-[4-[2-methoxy-4-[(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)OC)=CC=C1CC1C(=O)NC(=S)S1 ZUWYXYIQUCLKTP-PDFNFFLASA-N 0.000 description 1
- ACHXYLPDZFRNPO-KHTASDDNSA-N methyl (2s)-2-amino-3-[4-[3-chloro-4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1Cl)=CC=C1CC1C(=O)NC(=O)S1 ACHXYLPDZFRNPO-KHTASDDNSA-N 0.000 description 1
- HEBGFSVSNPGKLW-KHTASDDNSA-N methyl (2s)-2-amino-3-[4-[3-chloro-4-[(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1Cl)=CC=C1CC1C(=O)NC(=S)S1 HEBGFSVSNPGKLW-KHTASDDNSA-N 0.000 description 1
- NFZVMKVAELFXOY-KHTASDDNSA-N methyl (2s)-2-amino-3-[4-[3-fluoro-4-[(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1F)=CC=C1CC1C(=O)NC(=S)S1 NFZVMKVAELFXOY-KHTASDDNSA-N 0.000 description 1
- DMTUTDFHIILGJM-YOXMSGLASA-N methyl (2s)-2-amino-3-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]-2-fluorophenoxy]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)F)=CC=C1CC1C(=O)NC(=O)S1 DMTUTDFHIILGJM-YOXMSGLASA-N 0.000 description 1
- MKYCWHRNFZWIEG-PDFNFFLASA-N methyl (2s)-2-amino-3-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]-2-methoxyphenoxy]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C(=C1)OC)=CC=C1CC1C(=O)NC(=O)S1 MKYCWHRNFZWIEG-PDFNFFLASA-N 0.000 description 1
- GNTFRLNUWOKLDO-KHTASDDNSA-N methyl (2s)-2-amino-3-[4-[4-[(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-yl)methyl]-3-(trifluoromethyl)phenoxy]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1C(F)(F)F)=CC=C1CC1C(=O)NC(=S)S1 GNTFRLNUWOKLDO-KHTASDDNSA-N 0.000 description 1
- IGLUNGXBEXOMNQ-INIZCTEOSA-N methyl (2s)-2-amino-3-[4-[4-[(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]phenoxy]phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC(C=C1)=CC=C1C=C1C(=O)NC(=S)S1 IGLUNGXBEXOMNQ-INIZCTEOSA-N 0.000 description 1
- AJBKFFDADWOQIZ-UHFFFAOYSA-N methyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[4-[4-[(2-oxo-1h-indol-3-ylidene)methyl]phenoxy]phenyl]propanoate Chemical compound C1=CC(CC(C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1OC(C=C1)=CC=C1C=C1C2=CC=CC=C2NC1=O AJBKFFDADWOQIZ-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- AHKJGIUKIBGOKH-UHFFFAOYSA-N morpholine;piperidine Chemical class C1CCNCC1.C1COCCN1 AHKJGIUKIBGOKH-UHFFFAOYSA-N 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- ACFIXJIJDZMPPO-NCHANQSKSA-N nadph Chemical compound C1=CCC(C(=O)N)=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](COP(O)(=O)OP(O)(=O)OC[C@H]2[C@@H]([C@H](OP(O)(O)=O)[C@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NCHANQSKSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100001092 no hepatotoxicity Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 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
- 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
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- RAIYODFGMLZUDF-UHFFFAOYSA-N piperidin-1-ium;acetate Chemical compound CC([O-])=O.C1CC[NH2+]CC1 RAIYODFGMLZUDF-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical class COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 231100000617 superantigen Toxicity 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/34—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/36—Sulfur atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Transplantation (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Ophthalmology & Optometry (AREA)
- Child & Adolescent Psychology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN347DE2005 | 2005-02-17 | ||
| IN347/DEL/2005 | 2005-02-17 | ||
| US11/096,718 | 2005-03-31 | ||
| US11/096,718 US7521465B2 (en) | 2003-01-17 | 2005-03-31 | Diphenyl ether derivatives |
| PCT/US2006/005846 WO2006089225A1 (en) | 2005-02-17 | 2006-02-17 | 5- [4- (4- (2 -amino- 2 -methoxycarbonylethyl) phenoxy) benzilidene] thiazolidin-2 , 4-dion e derivatives and related compounds for reducing glucose, cholesterol and triglyceride levels in plasma |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2008530242A JP2008530242A (ja) | 2008-08-07 |
| JP2008530242A5 JP2008530242A5 (enExample) | 2009-04-16 |
| JP5134974B2 true JP5134974B2 (ja) | 2013-01-30 |
Family
ID=36570583
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007556366A Expired - Fee Related JP5134974B2 (ja) | 2005-02-17 | 2006-02-17 | 血漿中のグルコースレベル、コレステロールレベル及びトリグリセリドレベルを低下させるための５−［４−（４−（２−アミノ−２−メトキシカルボニルエチル）フェノキシ）ベンジリデン］チアゾリジン−２，４−ジオン誘導体及び関連化合物 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7521465B2 (enExample) |
| EP (1) | EP1848700B1 (enExample) |
| JP (1) | JP5134974B2 (enExample) |
| KR (1) | KR20070105364A (enExample) |
| CA (1) | CA2598087C (enExample) |
| ES (1) | ES2566337T3 (enExample) |
| HU (1) | HUE028882T2 (enExample) |
| PL (1) | PL1848700T3 (enExample) |
| WO (1) | WO2006089225A1 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9969980B2 (en) * | 2001-09-21 | 2018-05-15 | Garnet Biotherapeutics | Cell populations which co-express CD49c and CD90 |
| US9969977B2 (en) * | 2002-09-20 | 2018-05-15 | Garnet Biotherapeutics | Cell populations which co-express CD49c and CD90 |
| US7521465B2 (en) | 2003-01-17 | 2009-04-21 | Bexel Pharmaceuticals, Inc. | Diphenyl ether derivatives |
| US7781464B2 (en) * | 2003-01-17 | 2010-08-24 | Bexel Pharmaceuticals, Inc. | Heterocyclic diphenyl ethers |
| US7087576B2 (en) * | 2003-10-07 | 2006-08-08 | Bexel Pharmaceuticals, Inc. | Dipeptide phenyl ethers |
| KR100814109B1 (ko) | 2006-01-09 | 2008-03-14 | 한국생명공학연구원 | 로다닌 유도체, 이의 제조방법 및 이를 유효성분으로함유하는 약학적 조성물 |
| US7989480B2 (en) * | 2006-08-04 | 2011-08-02 | Decode Genetics Ehf | Aryl amino acid derivatives as inhibitors for treating inflammation |
| US20090069313A1 (en) * | 2007-09-06 | 2009-03-12 | Orchid Research Laboratories Ltd. | Novel MAO-A inhibitors |
| ATE536347T1 (de) | 2008-05-20 | 2011-12-15 | Merck Sharp & Dohme | Effiziente herstellung heterologer proteine unter verwendung von mannosyltransferaseinhibitoren |
| US20140187594A1 (en) | 2010-07-28 | 2014-07-03 | Orchid Chemicals And Pharmaceuticals Ltd | Diphenyl ether compounds for the treatment of liver, lung disorders, diabetic complications and cardiovascular diseases |
| WO2012153775A1 (ja) | 2011-05-10 | 2012-11-15 | 国立大学法人神戸大学 | Ras機能阻害作用を有するチオキソチアゾリジン誘導体 |
| EP4029859A1 (en) | 2014-11-21 | 2022-07-20 | Bsim Therapeutics, S.A. | 2-oxothiazolidin-4-one derivatives active as transthyretin ligands and uses thereof |
| TW202019923A (zh) * | 2018-07-16 | 2020-06-01 | 義大利商吉斯藥品公司 | 作為Ｒｈｏ－激酶抑制劑之酪胺酸醯胺衍生物 |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0228168A (ja) * | 1988-04-14 | 1990-01-30 | Sankyo Co Ltd | チアゾール誘導体 |
| US20020049240A1 (en) | 1994-12-19 | 2002-04-25 | Beecham Group P.1.C. | Novel compounds |
| US5166137A (en) | 1991-03-27 | 1992-11-24 | Nobipols Forskningsstiftelse | Guluronic acid polymers and use of same for inhibition of cytokine production |
| US5441971A (en) | 1991-04-11 | 1995-08-15 | The Upjohn Company | Thiazolidinedione derivatives, production and use thereof |
| TW268952B (enExample) | 1993-02-26 | 1996-01-21 | Takeda Pharm Industry Co Ltd | |
| US5527546A (en) | 1994-08-10 | 1996-06-18 | Bayer Corporation | Human interleukin 6 inhibitor |
| ATE271128T1 (de) | 1995-05-11 | 2004-07-15 | Applied Research Systems | Inhibitoren der il-6 aktivitaet |
| TW577875B (en) | 1997-01-31 | 2004-03-01 | Shionogi & Co | Pyrrolidine derivatives with inhibitory activity for phospholipase A2 |
| US6331633B1 (en) | 1998-05-08 | 2001-12-18 | Calyx Therapeutics Inc. | Heterocyclic analogs of diphenylethylene compounds |
| US6699896B1 (en) | 1998-05-12 | 2004-03-02 | Wyeth | Oxazole-aryl-carboxylic acids useful in the treatment of insulin resistance and hyperglycemia |
| EP1082323A2 (en) | 1998-06-05 | 2001-03-14 | AstraZeneca UK Limited | Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them |
| WO2000000194A1 (en) | 1998-06-27 | 2000-01-06 | Photogenesis, Inc. | Ophthalmic uses of ppargamma agonists and ppargamma antagonists |
| EP1108713A4 (en) | 1998-08-27 | 2006-04-05 | Ono Pharmaceutical Co | CARBOXYLENE DERIVATIVES AND MEDICAMENTS CONTAINING THEM AS AN ACTIVE COMPONENT |
| HUP0200996A3 (en) | 1999-04-07 | 2003-01-28 | Sankyo Company Ltd Chuo Ku | Amine derivatives, pharmaceutical compositions containing them and their use |
| HRP20010795A2 (en) | 1999-04-28 | 2003-02-28 | Aventis Pharma Gmbh | Di-aryl acid derivatives as ppar receptor ligands |
| TWI284533B (en) | 1999-05-24 | 2007-08-01 | Sankyo Co | Pharmaceutical composition for treating hyperglycemia, impaired glucose tolerance, diabetes complications and for improving insulin resistant |
| ID29875A (id) | 1999-07-01 | 2001-10-18 | Geron Corp Cs | Penghambat-penghambat telomerase dan metode penggunaannya |
| US6730687B1 (en) | 1999-08-23 | 2004-05-04 | Kyorin Pharmaceutical Co., Ltd. | Substituted benzylthiazolidine-2, 4-dione derivatives |
| CN1384825A (zh) * | 1999-08-31 | 2002-12-11 | 马克西亚药品公司 | 亚苄基－噻唑烷二酮及其类似物以及它们在治疗糖尿病中的应用 |
| JP2001199888A (ja) | 2000-01-24 | 2001-07-24 | Fujimoto Brothers:Kk | 糖尿病治療剤 |
| JP2001308814A (ja) | 2000-04-19 | 2001-11-02 | Hitachi Ltd | フレーム構成自動識別通信装置 |
| DE60115132T2 (de) | 2000-04-21 | 2006-07-06 | Pfizer Products Inc., Groton | Thyroid-Rezeptorliganden |
| US6620830B2 (en) | 2000-04-21 | 2003-09-16 | Pfizer, Inc. | Thyroid receptor ligands |
| US6680387B2 (en) | 2000-04-24 | 2004-01-20 | Aryx Therapeutics | Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis |
| US6525202B2 (en) * | 2000-07-17 | 2003-02-25 | Wyeth | Cyclic amine phenyl beta-3 adrenergic receptor agonists |
| ATE363278T1 (de) | 2001-09-14 | 2007-06-15 | Novo Nordisk As | Neue liganden für die hisb10 zn2+ stellen des insulin-hexamers in der r-konformation |
| JP2005513026A (ja) * | 2001-11-15 | 2005-05-12 | インサイト サン ディエゴ インコーポレイテッド | 高コレステロール血症、異脂肪血症および他の代謝障害；癌、および他の疾患を治療するｎ−置換複素環 |
| US7521465B2 (en) | 2003-01-17 | 2009-04-21 | Bexel Pharmaceuticals, Inc. | Diphenyl ether derivatives |
| US6794401B2 (en) | 2003-01-17 | 2004-09-21 | Bexel Pharmaceuticals, Inc. | Amino acid phenoxy ethers |
| JP2007523842A (ja) | 2003-03-11 | 2007-08-23 | ノボ ノルディスク アクティーゼルスカブ | 酸安定化されたインスリンを含有する薬学的製剤 |
| US7087576B2 (en) | 2003-10-07 | 2006-08-08 | Bexel Pharmaceuticals, Inc. | Dipeptide phenyl ethers |
-
2005
- 2005-03-31 US US11/096,718 patent/US7521465B2/en not_active Expired - Fee Related
-
2006
- 2006-02-17 HU HUE06735487A patent/HUE028882T2/en unknown
- 2006-02-17 KR KR1020077021343A patent/KR20070105364A/ko not_active Ceased
- 2006-02-17 JP JP2007556366A patent/JP5134974B2/ja not_active Expired - Fee Related
- 2006-02-17 PL PL06735487T patent/PL1848700T3/pl unknown
- 2006-02-17 ES ES06735487.8T patent/ES2566337T3/es not_active Expired - Lifetime
- 2006-02-17 EP EP06735487.8A patent/EP1848700B1/en not_active Expired - Lifetime
- 2006-02-17 WO PCT/US2006/005846 patent/WO2006089225A1/en not_active Ceased
- 2006-02-17 CA CA2598087A patent/CA2598087C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP1848700B1 (en) | 2015-12-30 |
| US7521465B2 (en) | 2009-04-21 |
| CA2598087A1 (en) | 2006-08-24 |
| US20050288341A1 (en) | 2005-12-29 |
| WO2006089225A1 (en) | 2006-08-24 |
| CA2598087C (en) | 2014-05-27 |
| PL1848700T3 (pl) | 2016-08-31 |
| HUE028882T2 (en) | 2017-01-30 |
| JP2008530242A (ja) | 2008-08-07 |
| ES2566337T3 (es) | 2016-04-12 |
| EP1848700A1 (en) | 2007-10-31 |
| KR20070105364A (ko) | 2007-10-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2008530242A (ja) | 血漿中のグルコースレベル、コレステロールレベル及びトリグリセリドレベルを低下させるための５−［４−（４−（２−アミノ−２−メトキシカルボニルエチル）フェノキシ）ベンジリデン］チアゾリジン−２，４−ジオン誘導体及び関連化合物 | |
| CA2642650C (en) | Novel heterocyclic diphenyl ethers | |
| AU2001266670B9 (en) | Novel heterocyclic analogs of diphenylethylene compounds | |
| JP4833072B2 (ja) | アミノ酸フェノキシエーテル | |
| US7521466B2 (en) | Dipeptide phenyl ethers | |
| US20080319031A1 (en) | Novel Tyrosine Derivatives | |
| CN101160296A (zh) | 用于降低血浆中葡萄糖、胆固醇和甘油三酸酯水平的5-[4-(4-(2-氨基-2-甲氧基羰基乙基)苯氧基)亚苄基]噻唑烷-2，4-二酮衍生物和相关化合物 | |
| JP2008535904A (ja) | 新規複素環誘導体 | |
| ZA200506527B (en) | Amino acid phenoxy ethers |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090217 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090217 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111003 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20111005 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20111227 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120110 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120322 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120611 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120911 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20121105 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20121112 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20151116 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 5134974 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |