CN100344616C - 用于治疗代谢失调的化合物 - Google Patents
用于治疗代谢失调的化合物 Download PDFInfo
- Publication number
- CN100344616C CN100344616C CNB028118812A CN02811881A CN100344616C CN 100344616 C CN100344616 C CN 100344616C CN B028118812 A CNB028118812 A CN B028118812A CN 02811881 A CN02811881 A CN 02811881A CN 100344616 C CN100344616 C CN 100344616C
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- phenyl
- carbon atom
- alkyl
- 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 abstract description 982
- 238000011282 treatment Methods 0.000 title claims abstract description 61
- 208000030159 metabolic disease Diseases 0.000 title abstract description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 71
- 208000008589 Obesity Diseases 0.000 claims abstract description 34
- 235000020824 obesity Nutrition 0.000 claims abstract description 31
- 208000010706 fatty liver disease Diseases 0.000 claims abstract description 23
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 15
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 12
- 208000031773 Insulin resistance syndrome Diseases 0.000 claims abstract description 11
- 206010006895 Cachexia Diseases 0.000 claims abstract description 10
- 206010003210 Arteriosclerosis Diseases 0.000 claims abstract description 7
- 208000011775 arteriosclerosis disease Diseases 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims description 454
- 125000004432 carbon atom Chemical group C* 0.000 claims description 397
- 229910052799 carbon Inorganic materials 0.000 claims description 324
- 125000000217 alkyl group Chemical group 0.000 claims description 233
- 239000003814 drug Substances 0.000 claims description 189
- 238000000034 method Methods 0.000 claims description 184
- 229910052739 hydrogen Inorganic materials 0.000 claims description 170
- 239000001257 hydrogen Substances 0.000 claims description 167
- 238000002360 preparation method Methods 0.000 claims description 159
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 110
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 110
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 98
- -1 methoxyl group Chemical group 0.000 claims description 98
- 229910052736 halogen Inorganic materials 0.000 claims description 95
- 150000002367 halogens Chemical class 0.000 claims description 95
- 125000003545 alkoxy group Chemical group 0.000 claims description 80
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 71
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 65
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 64
- 239000002253 acid Substances 0.000 claims description 62
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 52
- 229910052731 fluorine Inorganic materials 0.000 claims description 50
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 50
- 239000011737 fluorine Substances 0.000 claims description 49
- 150000003839 salts Chemical class 0.000 claims description 40
- 239000003513 alkali Substances 0.000 claims description 39
- 239000011734 sodium Substances 0.000 claims description 39
- 239000000460 chlorine Substances 0.000 claims description 35
- 230000007062 hydrolysis Effects 0.000 claims description 33
- 238000006460 hydrolysis reaction Methods 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 33
- 229910052801 chlorine Inorganic materials 0.000 claims description 29
- 239000002585 base Substances 0.000 claims description 27
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 21
- 206010022489 Insulin Resistance Diseases 0.000 claims description 20
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 150000001408 amides Chemical class 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- UIUJIQZEACWQSV-UHFFFAOYSA-N succinic semialdehyde Chemical compound OC(=O)CCC=O UIUJIQZEACWQSV-UHFFFAOYSA-N 0.000 claims description 12
- 208000002177 Cataract Diseases 0.000 claims description 10
- 239000012867 bioactive agent Substances 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- 208000026500 emaciation Diseases 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- 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 claims description 5
- 208000017442 Retinal disease Diseases 0.000 claims description 5
- 206010038923 Retinopathy Diseases 0.000 claims description 5
- 208000025865 Ulcer Diseases 0.000 claims description 5
- 150000007513 acids Chemical class 0.000 claims description 5
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- 231100000397 ulcer Toxicity 0.000 claims description 5
- IDBQCNOWFLIFPM-UHFFFAOYSA-N 4-[3-[(2,6-difluorophenyl)methoxy]phenyl]-4-oxobutanoic acid Chemical class OC(=O)CCC(=O)C1=CC=CC(OCC=2C(=CC=CC=2F)F)=C1 IDBQCNOWFLIFPM-UHFFFAOYSA-N 0.000 claims description 4
- FMWZELKYUWYZRY-UHFFFAOYSA-N 4-[3-[(2-fluoro-6-methylphenyl)methoxy]phenyl]-4-oxobutanoic acid Chemical class CC1=CC=CC(F)=C1COC1=CC=CC(C(=O)CCC(O)=O)=C1 FMWZELKYUWYZRY-UHFFFAOYSA-N 0.000 claims description 4
- RKNUZODTBHBVDS-UHFFFAOYSA-N 4-[4-[(2,6-difluorophenyl)methoxy]phenyl]-4-oxobutanoic acid Chemical class C1=CC(C(=O)CCC(=O)O)=CC=C1OCC1=C(F)C=CC=C1F RKNUZODTBHBVDS-UHFFFAOYSA-N 0.000 claims description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000011591 potassium Substances 0.000 claims description 4
- 159000000000 sodium salts Chemical class 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- PYEMFJAZILFLEZ-UHFFFAOYSA-N 4-[2-[(2,6-difluorophenyl)methoxy]phenyl]-4-oxobutanoic acid Chemical class OC(=O)CCC(=O)C1=CC=CC=C1OCC1=C(F)C=CC=C1F PYEMFJAZILFLEZ-UHFFFAOYSA-N 0.000 claims description 3
- GMSFOWMGHGGASO-UHFFFAOYSA-N 4-[3-[(2,6-dimethoxyphenyl)methoxy]phenyl]-4-oxobutanoic acid Chemical class COC1=CC=CC(OC)=C1COC1=CC=CC(C(=O)CCC(O)=O)=C1 GMSFOWMGHGGASO-UHFFFAOYSA-N 0.000 claims description 3
- BPNPEIBOTNDLQS-UHFFFAOYSA-N 4-[3-[(2-methylphenyl)methoxy]phenyl]-4-oxobutanoic acid Chemical class CC1=CC=CC=C1COC1=CC=CC(C(=O)CCC(O)=O)=C1 BPNPEIBOTNDLQS-UHFFFAOYSA-N 0.000 claims description 3
- YWICWJIZWROWLT-UHFFFAOYSA-N 4-[4-[(2,4-difluorophenyl)methoxy]phenyl]-4-oxobutanoic acid Chemical class C1=CC(C(=O)CCC(=O)O)=CC=C1OCC1=CC=C(F)C=C1F YWICWJIZWROWLT-UHFFFAOYSA-N 0.000 claims description 3
- IIMUHSVNELGECO-UHFFFAOYSA-N 4-[4-[(2,5-difluorophenyl)methoxy]phenyl]-4-oxobutanoic acid Chemical class C1=CC(C(=O)CCC(=O)O)=CC=C1OCC1=CC(F)=CC=C1F IIMUHSVNELGECO-UHFFFAOYSA-N 0.000 claims description 3
- YADLQEFRHHBMGQ-UHFFFAOYSA-N 4-[4-[(2-methylphenyl)methoxy]phenyl]-4-oxobutanoic acid Chemical class CC1=CC=CC=C1COC1=CC=C(C(=O)CCC(O)=O)C=C1 YADLQEFRHHBMGQ-UHFFFAOYSA-N 0.000 claims description 3
- BASURFQVOZJAFE-UHFFFAOYSA-N 4-oxo-4-(4-phenylmethoxyphenyl)butanoic acid Chemical class C1=CC(C(=O)CCC(=O)O)=CC=C1OCC1=CC=CC=C1 BASURFQVOZJAFE-UHFFFAOYSA-N 0.000 claims description 3
- PQESJEIAPIVSIE-UHFFFAOYSA-N 4-oxo-4-[3-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]butanoic acid Chemical class OC(=O)CCC(=O)C1=CC=CC(OCC=2C=CC(=CC=2)C(F)(F)F)=C1 PQESJEIAPIVSIE-UHFFFAOYSA-N 0.000 claims description 3
- ZGYBTRJTTITVRP-UHFFFAOYSA-N 4-oxo-4-[4-[[2-(trifluoromethyl)phenyl]methoxy]phenyl]butanoic acid Chemical class C1=CC(C(=O)CCC(=O)O)=CC=C1OCC1=CC=CC=C1C(F)(F)F ZGYBTRJTTITVRP-UHFFFAOYSA-N 0.000 claims description 3
- 238000006751 Mitsunobu reaction Methods 0.000 claims description 3
- 238000011161 development Methods 0.000 claims description 3
- LOFPPLZWUJAFSF-UHFFFAOYSA-N ethyl 4-[4-[(2,6-difluorophenyl)methoxy]phenyl]-4-oxobutanoate Chemical class C1=CC(C(=O)CCC(=O)OCC)=CC=C1OCC1=C(F)C=CC=C1F LOFPPLZWUJAFSF-UHFFFAOYSA-N 0.000 claims description 3
- DDRNZSBOEUQHSX-UHFFFAOYSA-N ethyl 4-[4-[(2-methylphenyl)methoxy]phenyl]-4-oxobutanoate Chemical class C1=CC(C(=O)CCC(=O)OCC)=CC=C1OCC1=CC=CC=C1C DDRNZSBOEUQHSX-UHFFFAOYSA-N 0.000 claims description 3
- 201000001119 neuropathy Diseases 0.000 claims description 3
- 230000007823 neuropathy Effects 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 229910052728 basic metal Inorganic materials 0.000 claims description 2
- 150000003818 basic metals Chemical class 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 230000003301 hydrolyzing effect Effects 0.000 claims 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 143
- 238000005160 1H NMR spectroscopy Methods 0.000 description 139
- 239000000243 solution Substances 0.000 description 82
- 241000699666 Mus <mouse, genus> Species 0.000 description 73
- 239000002994 raw material Substances 0.000 description 68
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
- 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 56
- 230000008859 change Effects 0.000 description 53
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 49
- 210000004369 blood Anatomy 0.000 description 48
- 239000008280 blood Substances 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 44
- 102000004877 Insulin Human genes 0.000 description 43
- 108090001061 Insulin Proteins 0.000 description 43
- 235000019439 ethyl acetate Nutrition 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
- 238000010898 silica gel chromatography Methods 0.000 description 41
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- 230000002194 synthesizing effect Effects 0.000 description 35
- 238000003756 stirring Methods 0.000 description 33
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 32
- 239000003795 chemical substances by application Substances 0.000 description 30
- 125000001072 heteroaryl group Chemical group 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- 239000012044 organic layer Substances 0.000 description 29
- 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 28
- 229960004586 rosiglitazone Drugs 0.000 description 28
- 239000007787 solid Substances 0.000 description 28
- 230000000694 effects Effects 0.000 description 26
- 238000010931 ester hydrolysis Methods 0.000 description 26
- 239000008103 glucose Substances 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- 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 24
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 24
- 210000002966 serum Anatomy 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- 230000003203 everyday effect Effects 0.000 description 22
- 238000001035 drying Methods 0.000 description 21
- 235000021588 free fatty acids Nutrition 0.000 description 21
- 235000013305 food Nutrition 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 201000001421 hyperglycemia Diseases 0.000 description 18
- 210000004185 liver Anatomy 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 17
- 229910052760 oxygen Inorganic materials 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 15
- 239000012141 concentrate Substances 0.000 description 15
- 238000004090 dissolution Methods 0.000 description 15
- 150000002148 esters Chemical class 0.000 description 15
- 239000003960 organic solvent Substances 0.000 description 15
- LUJMEECXHPYQOF-UHFFFAOYSA-N 3-hydroxyacetophenone Chemical compound CC(=O)C1=CC=CC(O)=C1 LUJMEECXHPYQOF-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 230000037396 body weight Effects 0.000 description 14
- 229940125396 insulin Drugs 0.000 description 14
- 208000024891 symptom Diseases 0.000 description 14
- 238000005406 washing Methods 0.000 description 14
- 108010092277 Leptin Proteins 0.000 description 13
- 238000009833 condensation Methods 0.000 description 13
- 230000005494 condensation Effects 0.000 description 13
- 150000002632 lipids Chemical class 0.000 description 13
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 12
- 102000016267 Leptin Human genes 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- 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 12
- 229940039781 leptin Drugs 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 238000012545 processing Methods 0.000 description 12
- 239000012266 salt solution Substances 0.000 description 12
- 108010082126 Alanine transaminase Proteins 0.000 description 11
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 11
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 11
- 206010019133 Hangover Diseases 0.000 description 11
- 239000003981 vehicle Substances 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 239000012300 argon atmosphere Substances 0.000 description 10
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 125000005842 heteroatom Chemical group 0.000 description 10
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 10
- 229910052717 sulfur Inorganic materials 0.000 description 10
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- 239000013543 active substance Substances 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 230000003178 anti-diabetic effect Effects 0.000 description 9
- 230000032050 esterification Effects 0.000 description 9
- 238000005886 esterification reaction Methods 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 230000002459 sustained effect Effects 0.000 description 9
- 238000010792 warming Methods 0.000 description 9
- 206010019708 Hepatic steatosis Diseases 0.000 description 8
- 230000029936 alkylation Effects 0.000 description 8
- 238000005804 alkylation reaction Methods 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 238000005893 bromination reaction Methods 0.000 description 8
- 230000001684 chronic effect Effects 0.000 description 8
- 235000005911 diet Nutrition 0.000 description 8
- 230000037213 diet Effects 0.000 description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- 208000004930 Fatty Liver Diseases 0.000 description 7
- 208000013016 Hypoglycemia Diseases 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 150000001718 carbodiimides Chemical class 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 210000000496 pancreas Anatomy 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 231100000240 steatosis hepatitis Toxicity 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 229940073735 4-hydroxy acetophenone Drugs 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 230000002218 hypoglycaemic effect Effects 0.000 description 6
- 238000005286 illumination Methods 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- 238000013293 zucker diabetic fatty rat Methods 0.000 description 6
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000003472 antidiabetic agent Substances 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003810 ethyl acetate extraction Methods 0.000 description 5
- 125000004494 ethyl ester group Chemical group 0.000 description 5
- 229960004580 glibenclamide Drugs 0.000 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 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 5
- 230000001771 impaired effect Effects 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 241000700157 Rattus norvegicus Species 0.000 description 4
- DQJWAWZJZGBCGQ-UHFFFAOYSA-N [O].CS(O)(=O)=O Chemical compound [O].CS(O)(=O)=O DQJWAWZJZGBCGQ-UHFFFAOYSA-N 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 150000001266 acyl halides Chemical class 0.000 description 4
- 150000001350 alkyl halides Chemical class 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000007269 dehydrobromination reaction Methods 0.000 description 4
- 201000005577 familial hyperlipidemia Diseases 0.000 description 4
- 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 description 4
- 229960002297 fenofibrate Drugs 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- 201000008980 hyperinsulinism Diseases 0.000 description 4
- 210000004153 islets of langerhan Anatomy 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000005229 liver cell Anatomy 0.000 description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 4
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 235000019260 propionic acid Nutrition 0.000 description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 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 description 3
- 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 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229940123208 Biguanide Drugs 0.000 description 3
- 208000032841 Bulimia Diseases 0.000 description 3
- 206010006550 Bulimia nervosa Diseases 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 3
- 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 description 3
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 3
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 3
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical group CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229960002632 acarbose Drugs 0.000 description 3
- 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 description 3
- WZSDNEJJUSYNSG-UHFFFAOYSA-N azocan-1-yl-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CCCCCCC2)=C1 WZSDNEJJUSYNSG-UHFFFAOYSA-N 0.000 description 3
- 150000004283 biguanides Chemical class 0.000 description 3
- 238000005660 chlorination reaction Methods 0.000 description 3
- 208000019425 cirrhosis of liver Diseases 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 3
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 3
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
- 230000004761 fibrosis Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000002641 glycemic effect Effects 0.000 description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
- 206010020718 hyperplasia Diseases 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 206010025482 malaise Diseases 0.000 description 3
- 235000012054 meals Nutrition 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 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 description 3
- 229960002965 pravastatin Drugs 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229960002354 repaglinide Drugs 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- QSSXJPIWXQTSIX-UHFFFAOYSA-N 1-bromo-2-methylbenzene Chemical compound CC1=CC=CC=C1Br QSSXJPIWXQTSIX-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- AFBBKYQYNPNMAT-UHFFFAOYSA-N 1h-1,2,4-triazol-1-ium-3-thiolate Chemical compound SC=1N=CNN=1 AFBBKYQYNPNMAT-UHFFFAOYSA-N 0.000 description 2
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 2
- MBKJMQVCYJTSQC-UHFFFAOYSA-N 2-[4-[(2,6-difluorophenyl)methoxy]phenyl]acetyl chloride Chemical compound FC1=CC=CC(F)=C1COC1=CC=C(CC(Cl)=O)C=C1 MBKJMQVCYJTSQC-UHFFFAOYSA-N 0.000 description 2
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
- 102000004420 Creatine Kinase Human genes 0.000 description 2
- 108010042126 Creatine kinase Proteins 0.000 description 2
- 208000007530 Essential hypertension Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 229940122355 Insulin sensitizer Drugs 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229940100389 Sulfonylurea Drugs 0.000 description 2
- 102000003929 Transaminases Human genes 0.000 description 2
- 108090000340 Transaminases Proteins 0.000 description 2
- MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 description 2
- MNZMECMQTYGSOI-UHFFFAOYSA-N acetic acid;hydron;bromide Chemical compound Br.CC(O)=O MNZMECMQTYGSOI-UHFFFAOYSA-N 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 2
- 230000001612 cachectic effect Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 2
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000005611 electricity Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 230000000058 esterolytic effect Effects 0.000 description 2
- 229960003750 ethyl chloride Drugs 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- NEXSMEBSBIABKL-UHFFFAOYSA-N hexamethyldisilane Chemical compound C[Si](C)(C)[Si](C)(C)C NEXSMEBSBIABKL-UHFFFAOYSA-N 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- 235000003642 hunger Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 230000037356 lipid metabolism Effects 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229960004844 lovastatin Drugs 0.000 description 2
- 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 description 2
- 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 description 2
- 239000000463 material Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 238000005649 metathesis reaction Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000002831 pharmacologic agent Substances 0.000 description 2
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000001235 sensitizing effect Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 229960002855 simvastatin Drugs 0.000 description 2
- 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 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- SFFKUZPNDPDSSE-UHFFFAOYSA-N tert-butyl 4-oxobutanoate Chemical compound CC(C)(C)OC(=O)CCC=O SFFKUZPNDPDSSE-UHFFFAOYSA-N 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- SBNOMDMPZCJYFR-UHFFFAOYSA-N (2,4-difluorophenyl)methyl hypobromite Chemical compound FC1=C(COBr)C=CC(=C1)F SBNOMDMPZCJYFR-UHFFFAOYSA-N 0.000 description 1
- JPEYJQDKTDVJSZ-UHFFFAOYSA-N (2,6-dimethylphenyl)methanol Chemical compound CC1=CC=CC(C)=C1CO JPEYJQDKTDVJSZ-UHFFFAOYSA-N 0.000 description 1
- WYLYBQSHRJMURN-UHFFFAOYSA-N (2-methoxyphenyl)methanol Chemical compound COC1=CC=CC=C1CO WYLYBQSHRJMURN-UHFFFAOYSA-N 0.000 description 1
- MEIRRNXMZYDVDW-MQQKCMAXSA-N (2E,4E)-2,4-hexadien-1-ol Chemical compound C\C=C\C=C\CO MEIRRNXMZYDVDW-MQQKCMAXSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-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
- VGIIILXIQLXVLC-UHFFFAOYSA-N 1-(2,6-difluorophenyl)ethanone Chemical compound CC(=O)C1=C(F)C=CC=C1F VGIIILXIQLXVLC-UHFFFAOYSA-N 0.000 description 1
- TXVVVEUSVBLDED-UHFFFAOYSA-N 1-(bromomethyl)-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1CBr TXVVVEUSVBLDED-UHFFFAOYSA-N 0.000 description 1
- FFWQLZFIMNTUCZ-UHFFFAOYSA-N 1-(bromomethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CBr FFWQLZFIMNTUCZ-UHFFFAOYSA-N 0.000 description 1
- WGVYCXYGPNNUQA-UHFFFAOYSA-N 1-(bromomethyl)-2-methylbenzene Chemical compound CC1=CC=CC=C1CBr WGVYCXYGPNNUQA-UHFFFAOYSA-N 0.000 description 1
- SCBZBMXPJYMXRC-UHFFFAOYSA-N 1-(bromomethyl)-3-fluorobenzene Chemical compound FC1=CC=CC(CBr)=C1 SCBZBMXPJYMXRC-UHFFFAOYSA-N 0.000 description 1
- IKSNDOVDVVPSMA-UHFFFAOYSA-N 1-(bromomethyl)-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(CBr)C=C1 IKSNDOVDVVPSMA-UHFFFAOYSA-N 0.000 description 1
- NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 1
- XZKFBZOAIGFZSU-UHFFFAOYSA-N 1-bromo-4-methylpentane Chemical compound CC(C)CCCBr XZKFBZOAIGFZSU-UHFFFAOYSA-N 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- HNIGZVZDWCTFPR-UHFFFAOYSA-N 2-(2-fluorophenyl)ethanol Chemical compound OCCC1=CC=CC=C1F HNIGZVZDWCTFPR-UHFFFAOYSA-N 0.000 description 1
- PECXPZGFZFGDRD-UHFFFAOYSA-N 2-(chloromethyl)-1,4-dimethylbenzene Chemical compound CC1=CC=C(C)C(CCl)=C1 PECXPZGFZFGDRD-UHFFFAOYSA-N 0.000 description 1
- AHHXOFPMXFEISG-UHFFFAOYSA-N 2-[4-[(2,6-difluorophenyl)methoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OCC1=C(F)C=CC=C1F AHHXOFPMXFEISG-UHFFFAOYSA-N 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- ZWVHTXAYIKBMEE-UHFFFAOYSA-N 2-hydroxyacetophenone Chemical compound OCC(=O)C1=CC=CC=C1 ZWVHTXAYIKBMEE-UHFFFAOYSA-N 0.000 description 1
- VMJOFTHFJMLIKL-UHFFFAOYSA-N 2-thiophen-2-ylethanol Chemical compound OCCC1=CC=CS1 VMJOFTHFJMLIKL-UHFFFAOYSA-N 0.000 description 1
- PVEOYINWKBTPIZ-UHFFFAOYSA-N 3-Butenoic acid Natural products OC(=O)CC=C PVEOYINWKBTPIZ-UHFFFAOYSA-N 0.000 description 1
- 125000004917 3-methyl-2-butyl group Chemical group CC(C(C)*)C 0.000 description 1
- IWFUUSWOWAQPJA-UHFFFAOYSA-N 4-[4-[(2,6-difluorophenyl)methoxy]phenyl]-2-methyl-4-oxobutanoic acid Chemical compound FC1=C(COC2=CC=C(C=C2)C(CC(C(=O)O)C)=O)C(=CC=C1)F IWFUUSWOWAQPJA-UHFFFAOYSA-N 0.000 description 1
- HCEQQASHRRPQFE-UHFFFAOYSA-N 5-chloro-n-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]-2-methoxybenzamide;3-(diaminomethylidene)-1,1-dimethylguanidine;hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N.COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 HCEQQASHRRPQFE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 206010018473 Glycosuria Diseases 0.000 description 1
- 208000000857 Hepatic Insufficiency Diseases 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 1
- 206010022998 Irritability Diseases 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
- 206010067125 Liver injury Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010027336 Menstruation delayed Diseases 0.000 description 1
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 1
- LXYMJKFAJHOZRX-UHFFFAOYSA-N N1N=CN=C1.[S] Chemical compound N1N=CN=C1.[S] LXYMJKFAJHOZRX-UHFFFAOYSA-N 0.000 description 1
- 241001274216 Naso Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- BGQYTDTZTGQHHL-UHFFFAOYSA-N OC(C)=CC(C1=CC=C(C=C1)OCC1=C(C=CC=C1F)F)=O Chemical compound OC(C)=CC(C1=CC=C(C=C1)OCC1=C(C=CC=C1F)F)=O BGQYTDTZTGQHHL-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 229920001774 Perfluoroether Polymers 0.000 description 1
- 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 description 1
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
- 101000650578 Salmonella phage P22 Regulatory protein C3 Proteins 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- 101001040920 Triticum aestivum Alpha-amylase inhibitor 0.28 Proteins 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 238000005644 Wolff-Kishner reduction reaction Methods 0.000 description 1
- PRDBLLIPPDOICK-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]methanamine Chemical compound NCC1=CC=C(C(F)(F)F)C=C1 PRDBLLIPPDOICK-UHFFFAOYSA-N 0.000 description 1
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- FLHFTXCMKFVKRP-UHFFFAOYSA-N bromomethylcyclobutane Chemical compound BrCC1CCC1 FLHFTXCMKFVKRP-UHFFFAOYSA-N 0.000 description 1
- IAQRGUVFOMOMEM-UHFFFAOYSA-N butene Natural products CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-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
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 230000001335 demethylating effect Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 125000005594 diketone group Chemical group 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000011984 electrochemiluminescence immunoassay Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- CTIJUQSSLWHXGD-UHFFFAOYSA-N ethyl 4-[3-[(2-fluoro-6-methylphenyl)methoxy]phenyl]-4-oxobutanoate Chemical compound CCOC(=O)CCC(=O)C1=CC=CC(OCC=2C(=CC=CC=2C)F)=C1 CTIJUQSSLWHXGD-UHFFFAOYSA-N 0.000 description 1
- HIBHNYQUWZUXKU-UHFFFAOYSA-N ethyl 4-[4-[(2,5-difluorophenyl)methoxy]phenyl]-4-oxobutanoate Chemical compound C1=CC(C(=O)CCC(=O)OCC)=CC=C1OCC1=CC(F)=CC=C1F HIBHNYQUWZUXKU-UHFFFAOYSA-N 0.000 description 1
- QFMPHCGACBODIJ-UHFFFAOYSA-N ethyl 4-oxobutanoate Chemical compound CCOC(=O)CCC=O QFMPHCGACBODIJ-UHFFFAOYSA-N 0.000 description 1
- 235000020187 evaporated milk Nutrition 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940112611 glucovance Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000006749 inflammatory damage Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 125000005905 mesyloxy group Chemical group 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- JAGUQBROJZXCFZ-UHFFFAOYSA-N propylideneurea Chemical compound CCC=NC(N)=O JAGUQBROJZXCFZ-UHFFFAOYSA-N 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- IAQRGUVFOMOMEM-ONEGZZNKSA-N trans-but-2-ene Chemical compound C\C=C\C IAQRGUVFOMOMEM-ONEGZZNKSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000009978 visual deterioration Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/12—Formation or introduction of functional groups containing oxygen of carboxylic acid ester groups
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/10—Aromatic or araliphatic carboxylic acids, or thio analogues thereof; Derivatives thereof
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
-
- 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
-
- 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
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
-
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
-
- 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
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
- C07C217/14—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring
- C07C217/18—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted
- C07C217/22—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted by carbon atoms having at least two bonds to oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/40—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/44—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by unsaturated carbon chains
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/30—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms
- C07C233/31—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/47—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
- C07C235/76—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
- C07C235/78—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton the carbon skeleton containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/84—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
- C07C323/59—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton with acylated amino groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/90—Unsaturated compounds containing keto groups containing singly bound oxygen-containing groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/47—Preparation of carboxylic acid esters by telomerisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/734—Ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
Abstract
Description
组别 | 葡萄糖mg/dL | 甘油三酸酯mg/dL | 胆固醇mg/dL | 体重(g) |
未患糖尿病的+载体 | 138±6 | 88±9 | 88±0.6 | 21+0.6 |
患糖尿病的+载体 | 615±46 | 154±16 | 133±6 | 17.5+1.0 |
患糖尿病的+化合物AH | 207±12 | 62±7* | 82±2 | 21.7+0.8* |
组别 | 存活数 |
载体 | 0/5 |
匹格列酮,30mg/kg/天 | 2/5 |
化合物AH,250mg/kg/天 | 4/5 |
组别 | 葡萄糖±SEMmg/dL | 甘油三酸酯±SEMmg/dL | 游离脂肪酸±SEM微摩尔/升 |
ob/+ob/obAW-10AW-30AW-100AW-150AW-300PG-30PG-100RSG-1RSG-3RSG-10RSG-30 | 268.6±12.9384.2±53.8369.6±62.5280.2±46.7286±47.1188.6±28.8128.4±8.8188.2±21.4174.6±11.5142.75±8.8190.2±12.7188.24±21.4174.6±11.5 | 111.6±12.0106.6±2.909115.6±7.896.4±7.366.2±5.972.6±5.663.6±3.4111.2±7.595.2±4.8109.75±4.4107.8±3.8111.2±7.595.2±4.8 | 2216±197.43399±345.63697.4±357.82552.2±334.71476±82.11481±158.81452.6±111.12606±139.21983.4±66.12090.75±67.72317.6±85.32606.4±139.21983.4±66.1 |
组别 | ALT(UL)±SEM | AST(U/L)±SEM | SDH(U/L)±SEM |
非肥胖的糖尿病的2022-10AW-30AW-100AW-150AW-300PG-30PG-100RSG-1RSG-3RSG-10RSG-30 | 106.4±16.3447.2±63.4483.8±81.9320.2±46.2202.8±38.0149.2±15.6188.2±10.3713.6±80.6646.0±56.1668.8±42.9716.6±56.6713.6±80.5646.0±56.1 | 25.6±2.7645.6±104.8653.4±104.8399.6±74.4143.8±30.4185.8±26.0335.4±44.81024±88.7901.0±49.3798.0±73.8853.8±43.81024.0±88.7901.2±49.3 | 23.2±4.5745.8±102.4626.8±93.8333.0±66.9121.2±14.1166.2±20.0207.0±29.3782.0±70.6603.0±27.3644.5±51.6615.4±38.6782.0±70.6603.0±27.3 |
组别 | 体重增加的平均值(克) |
HPMC(载体) | +7.4 |
AW-3mg/kg/天 | +7.3 |
AW-10mg/kg/天 | +6.7 |
AW-30mg/kg/天 | +6.4 |
AW-100mg/kg/天 | +3.4 |
AW-150mg/kg/天 | +4.6 |
AW-300mg/kg/天 | -0.7 |
PG-30mg/kg/天 | +10.0 |
PG-100mg/kg/天 | +13.6 |
RSG-1mg/kg/天 | +8.2 |
RSG-3mg/kg/天 | +8.5 |
RSG-10mg/kg/天 | +11.0 |
RSG-30mg/kg/天 | +12.0 |
治疗组 | 6小时后的血糖 | 相对于对照组的下降百分数 |
载体 | 297±35 | 0.0±11.8 |
化合物AA | 242±25 | -18.5±8.4 |
化合物AB | 181±19 | -39.1±6.4 |
化合物AF | 314±32 | -24.6±7.7* |
化合物AG | 222±23 | -25.3±7.7 |
化合物AH | 223±11 | -24.9±3.7 |
化合物AI | 255±9 | -14.1±3.0 |
化合物AJ | 190±14 | -36.0±4.7 |
化合物AK | 210±10 | -29.3±3.4 |
化合物AL | 168±13 | -43.4±4.4 |
治疗组 | 6小时后的血糖mg/dL | 相对于对照组的下降百分数 |
载体对照 | 305±20 | 0.0±5.0 |
化合物AN | 152±11 | -50.2±4.5% |
化合物AQ | 220±17 | -27.9±4.2% |
化合物AR | 179±14 | -41.3±4.2% |
化合物AS | 167±28 | -45.2±2.0% |
化合物AT | 198±28 | -35.1±2.3% |
化合物AU | 224±26 | -26.6±2.8% |
化合物AV | 207±23 | -32.1±3.0% |
化合物AW | 143±15 | -53.1±3.1% |
化合物AX | 165±23 | -45.9±2.4% |
化合物AY | 185±21 | -39.3±2.9% |
化合物AZ | 186±10 | -39.0±6.1% |
组别 | 葡萄糖mg/dL | 葡萄糖(占对照组的%) |
载体(对照) | 562±24 | 100±4 |
化合物AW-150mg/kg | 313±34* | 56±6* |
化合物BH-150mg/kg | 229±49* | 41±9* |
匹格列酮-100mg/kg | 558±28 | 99±5 |
组别 | 葡萄糖(mg/dL) | 甘油三酸酯(mg/dL) |
载体(对照) | 686±47 | 147±13 |
罗格列酮-20mg/kg | 343±38* | 89±16* |
化合物BI-150mg/kg | 254±30* | 99±8* |
组别 | 葡萄糖mg/dL | 葡萄糖(占对照组的%) |
载体(对照) | 632±19 | 100±3 |
BI-150mg/kg | 297±35* | 44±6* |
BI-100mg/kg | 423±53* | 67±8* |
BO-100mg/kg | 586±58 | 93±9 |
BP-100mg/kg | 629±86 | 99±14 |
BQ-100mg/kg | 473±49* | 75±7* |
BR-82mg/kg | 703±64 | 111±10 |
组别 | 甘油三酸酯±SEM(mg/dL) | 游离脂肪酸±SEM(μM) |
非肥胖的 | 142.3±6.3 | 2577.6±80.8 |
糖尿病 | 444.3±57.3 | 4044.9±158.5 |
BI-150 | 103.6±8.3 | 2234.0±132.6 |
BI-100 | 134.0±13.1 | 2999.9±98.7 |
BO-100 | 261.1±24.3 | 3766.3±234.5 |
BP-100 | 302.1±28.1 | 3772.6±182.5 |
BQ-100 | 131.6±20.7 | 2825.9±110.9 |
BR-82 | 253.0±32.0 | 3653.4±207.5 |
组别 | 葡萄糖mg/dL | 葡萄糖(占对照组的%) |
载体(对照) | 692.5±55.4 | 100±8 |
BI-100mg/kg | 347.0±43.1* | 50±6* |
BS-93mg/kg | 372.0±53.8* | 54±8* |
BT-107mg/kg | 684.3±63.6 | 99±9 |
BU-128mg/kg | 533.3±46.7 | 77±7 |
BV-115mg/kg | 789.5±38.9 | 114±6 |
非诺贝特-113mg/kg | 563.2±49.0 | 81±7 |
组别 | 甘油三酸酯±SEM(mg/dL) | 游离脂肪酸±SEM(μM) |
非肥胖的 | 114.2±8.7 | 2315.8±238.3 |
载体 | 232.8±20.7 | 3511.8±257.6 |
BI | 77.8±5.3 | 1997.2±196.4 |
BS | 132.0±15.2 | 2867.4±267.7 |
BT | 211.5±21.5 | 3897.7±291.3 |
BU | 172.5±9.9 | 3587.0±156.3 |
BV | 153.2±14.2 | 3373.8±233.6 |
非诺贝特 | 109.3±9.1 | 3318.5±208.7 |
动物组别 | 白内障增生 | %保护 | |||
N | 左眼 | 右眼 | 左眼 | 右眼 | |
载体-对照BIBH非肥胖的 | 6664 | 6/63/64/60/4 | 6/61/65/60/4 | 05033无 | 08317无 |
组别 | 重量(mg) | 尺寸(mm) | 晶状体的MDAnmol/g晶状体 | ||
左眼 | 右眼 | 左眼 | 右眼 | ||
非肥胖的载体BIBH | 51.2±3.515.1±1.438.1±7.3**27.0±7.2 | 59.0±0.416.8±1.754.9±1.2*20.0±6.6 | 3.8±0.21.9±0.13.4±0.2*2.5±0.3 | 3.9±0.12.0±0.23.8±0.1*2.1±0.4 | 0.4±0.02.4±0.20.8±0.1#1.9±0.2 |
甘油三酸酯(mg/dL) | 游离脂肪酸(μmol/L) | |
载体 | 135±40.1 | 1686±359.3 |
BI(10mg/kg) | 68.8±5.7 | 1227±193.7 |
BI(30mg/kg) | 66.5±14.7 | 1292±231.4 |
BI(100mg/kg) | 37.4±8.3 | 992.8±172.1 |
BL(10mg/kg) | 80±12.2 | 1571.8±100.9 |
BL(30mg/kg) | 66.4±13.7 | 1413.2±228.7 |
BL(100mg/kg) | 41±5.6 | 1133.5±132.7 |
罗格列酮(1mg/kg) | 76.6±16.5 | 1537±256.3 |
罗格列酮(3mg/kg) | 103.2±10.8 | 1833.2±169.8 |
罗格列酮(10mg/kg) | 129.5±48.7 | 1810.3±595 |
罗格列酮(100mg/kg) | 88±7.2 | 1568.5±197 |
Wyl4643(10mg/kg) | 70.6±0.8 | 1512.2±172.9 |
Wyl4643(30mg/kg) | 88±12.5 | 1676±237 |
Wyl4643(100mg/kg) | 88.4±18.8 | 1839.8±154.8 |
罗格列酮(3mg/kg)+Wyl4643(100mg/kg) | 54.3±10.5 | 1649.7±260.5 |
组别 | 葡萄糖(mg/dL) | 胰岛素(ng/ml) | 甘油三酸酯(mg/dL) | 游离脂肪酸(μMol/L) |
非肥胖的 | 123.8±7.0 | 0.72±0.1 | 179.0±72.3 | 743.5±57.4 |
载体 | 122.3±5.9 | 1.78±0.3 | 200.7±39.2 | 942.5±181.0 |
BI-10 | 117.3±8.8 | 2.18±0.91 | 183.7±58.4 | 923.7±161.3 |
BI-30 | 127.3±22.2 | 1.46±0.2 | 129.3±20.0 | 738.7±50.0 |
BI-100 | 19.3±3.5 | 1.79±0.2 | 171.7±33.1 | 725.7±87.5 |
RG-3 | 119.8±5.4 | 1.57±0.2 | 134.2±15.2 | 758.8±61.0 |
Claims (97)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US29728201P | 2001-06-12 | 2001-06-12 | |
US60/297,282 | 2001-06-12 |
Related Child Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2007101492677A Division CN101444496B (zh) | 2001-06-12 | 2002-06-12 | 用于治疗代谢失调的化合物 |
CN2011100531191A Division CN102140064A (zh) | 2001-06-12 | 2002-06-12 | 用于治疗代谢失调的化合物 |
CN2011100525843A Division CN102151262A (zh) | 2001-06-12 | 2002-06-12 | 用于治疗代谢失调的化合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1608055A CN1608055A (zh) | 2005-04-20 |
CN100344616C true CN100344616C (zh) | 2007-10-24 |
Family
ID=23145636
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB028118812A Expired - Fee Related CN100344616C (zh) | 2001-06-12 | 2002-06-12 | 用于治疗代谢失调的化合物 |
CN2011100531191A Pending CN102140064A (zh) | 2001-06-12 | 2002-06-12 | 用于治疗代谢失调的化合物 |
CN2011100525843A Pending CN102151262A (zh) | 2001-06-12 | 2002-06-12 | 用于治疗代谢失调的化合物 |
CN2007101492677A Expired - Fee Related CN101444496B (zh) | 2001-06-12 | 2002-06-12 | 用于治疗代谢失调的化合物 |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2011100531191A Pending CN102140064A (zh) | 2001-06-12 | 2002-06-12 | 用于治疗代谢失调的化合物 |
CN2011100525843A Pending CN102151262A (zh) | 2001-06-12 | 2002-06-12 | 用于治疗代谢失调的化合物 |
CN2007101492677A Expired - Fee Related CN101444496B (zh) | 2001-06-12 | 2002-06-12 | 用于治疗代谢失调的化合物 |
Country Status (20)
Country | Link |
---|---|
US (23) | US7329782B2 (zh) |
EP (1) | EP1461323B1 (zh) |
JP (4) | JP4711621B2 (zh) |
KR (4) | KR100965201B1 (zh) |
CN (4) | CN100344616C (zh) |
AU (3) | AU2002345625B2 (zh) |
BR (1) | BRPI0210383B1 (zh) |
CA (1) | CA2450221C (zh) |
CZ (1) | CZ20033394A3 (zh) |
ES (1) | ES2441874T3 (zh) |
HK (2) | HK1076805A1 (zh) |
HU (1) | HU230352B1 (zh) |
IL (5) | IL159320A0 (zh) |
MX (1) | MXPA03011558A (zh) |
NO (2) | NO333355B1 (zh) |
NZ (1) | NZ530051A (zh) |
RU (2) | RU2341513C2 (zh) |
UA (2) | UA104987C2 (zh) |
WO (1) | WO2002100341A2 (zh) |
ZA (1) | ZA200309627B (zh) |
Families Citing this family (74)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6670358B2 (en) | 2000-05-16 | 2003-12-30 | Cephalon, Inc. | Substituted thioacetamides |
MXPA03011558A (es) * | 2001-06-12 | 2004-03-26 | Wellstat Therapeutics Corp | Compuestos para el tratamiento de desordenes metabolicos. |
CA2473232C (en) * | 2002-01-11 | 2011-03-15 | Abbott Laboratories | Histamine-3 receptor ligands for diabetic conditions |
US7645772B2 (en) | 2002-11-01 | 2010-01-12 | Wellstat Therapeutics Corporation | Treatment of metabolic disorders |
US7615575B2 (en) * | 2003-02-13 | 2009-11-10 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
SI1633340T1 (sl) * | 2003-04-15 | 2011-02-28 | Wellstat Therapeutics Corp | Spojine za zdravljenje metaboličnih motenj |
JP4697973B2 (ja) * | 2003-04-22 | 2011-06-08 | ウェルスタット セラピューティクス コーポレイション | 代謝障害の処置のための化合物 |
EA200501710A1 (ru) | 2003-04-30 | 2006-06-30 | ДЗЕ ИНСТИТЬЮТС ФОР ФАРМАСЬЮТИКАЛ ДИСКАВЕРИ, ЭлЭлСи | Замещённые карбоновые кислоты |
WO2004098496A2 (en) * | 2003-04-30 | 2004-11-18 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
US7348338B2 (en) * | 2003-07-17 | 2008-03-25 | Plexxikon, Inc. | PPAR active compounds |
NZ545326A (en) | 2003-07-17 | 2009-12-24 | Plexxikon Inc | PPAR active compounds |
US7906675B2 (en) * | 2003-08-20 | 2011-03-15 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
KR20070011329A (ko) * | 2004-03-29 | 2007-01-24 | 상꾜 가부시키가이샤 | 인슐린 저항성 개선제를 함유하는 당뇨병 치료제 |
EP1586560A1 (en) * | 2004-04-13 | 2005-10-19 | Cephalon, Inc. | Thio-substituted arylmethanesulfinyl derivatives |
US7297817B2 (en) * | 2004-04-13 | 2007-11-20 | Cephalon France | Thio-substituted arylmethanesulfinyl derivatives |
US7449481B2 (en) * | 2004-04-13 | 2008-11-11 | Cephalon, Inc. | Thio-substituted biaryl-methanesulfinyl derivatives |
US7119214B2 (en) | 2004-04-13 | 2006-10-10 | Cephalon France | Thio-substituted tricyclic and bicyclic aromatic methanesulfinyl derivatives |
US7314875B2 (en) * | 2004-04-13 | 2008-01-01 | Cephalon, Inc. | Tricyclic aromatic and bis-phenyl sulfinyl derivatives |
US7423176B2 (en) * | 2004-04-13 | 2008-09-09 | Cephalon, Inc. | Bicyclic aromatic sulfinyl derivatives |
JP2008518926A (ja) * | 2004-10-28 | 2008-06-05 | ジ インスティチューツ フォー ファーマシューティカル ディスカバリー、エルエルシー | 置換フェニルアルカン酸 |
US8394765B2 (en) * | 2004-11-01 | 2013-03-12 | Amylin Pharmaceuticals Llc | Methods of treating obesity with two different anti-obesity agents |
EP1819673A2 (en) * | 2004-11-30 | 2007-08-22 | Plexxikon, Inc. | Indole derivatives for use as ppar active compounds |
WO2006063294A2 (en) * | 2004-12-09 | 2006-06-15 | Kalypsys, Inc. | Novel inhibitors of histone deacetylase for the treatment of disease |
US8022249B2 (en) * | 2005-04-01 | 2011-09-20 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
EP1896027A4 (en) | 2005-06-10 | 2011-11-30 | Donald E Scott | TOPICAL COMPOSITIONS AND METHODS FOR TREATING OR INHIBITING SYMPTOMS RELATED TO CARPET TUNNEL SYNDROME, SURFACE FLUX, PSORIASIS, CANDLES, FIBROMYALGIA AND DIABETES |
CA2613522A1 (en) | 2005-06-27 | 2007-01-04 | Exelixis, Inc. | Imidazole based lxr modulators |
JP2009509932A (ja) * | 2005-09-07 | 2009-03-12 | プレキシコン,インコーポレーテッド | Ppar活性化合物 |
RU2419618C2 (ru) * | 2005-09-07 | 2011-05-27 | Плекссикон, Инк. | Соединения, активные в отношении ppar (рецепторов активаторов пролиферации пероксисом) |
TW200800872A (en) * | 2005-09-07 | 2008-01-01 | Plexxikon Inc | PPAR active compounds |
US20070074300A1 (en) * | 2005-09-28 | 2007-03-29 | Suleiman Igdoura | Sialidase inhibitors for the treatment of cardiovascular disease |
UA95613C2 (ru) * | 2005-11-09 | 2011-08-25 | Уеллстат Терепьютикс Корпорейшн | Соединения для лечения расстройсв метаболизма |
JP2009521452A (ja) * | 2005-12-21 | 2009-06-04 | シェーリング コーポレイション | コレステロール降下剤およびh3受容体アンタゴニスト/逆アゴニストを使用する非アルコール性脂肪性肝疾患の処置 |
US20070155707A1 (en) * | 2005-12-29 | 2007-07-05 | Kadmus Pharmaceuticals, Inc. | Ionizable inhibitors of fatty acid amide hydrolase |
US7947735B2 (en) | 2006-01-25 | 2011-05-24 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
CA2637373A1 (en) * | 2006-01-25 | 2007-08-02 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
CA2637375A1 (en) * | 2006-01-25 | 2007-08-02 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
KR20080097418A (ko) * | 2006-02-02 | 2008-11-05 | 웰스태트 테러퓨틱스 코포레이션 | 물질대사 장애의 치료용 화합물 |
CA2637884A1 (en) * | 2006-02-13 | 2007-08-23 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
KR20080098615A (ko) * | 2006-02-28 | 2008-11-11 | 웰스태트 테러퓨틱스 코포레이션 | 물질대사 장애의 치료용 화합물 |
AU2007235145B2 (en) * | 2006-03-31 | 2011-09-22 | Wellstat Therapeutics Corporation | Combination treatment of metabolic disorders |
US20070238183A1 (en) * | 2006-04-04 | 2007-10-11 | Stout Robert L | Methods for assessment of cardiovascular disease risk |
CN101437506A (zh) * | 2006-05-18 | 2009-05-20 | 维尔斯达医疗公司 | 用于治疗代谢紊乱的化合物 |
MX2008015640A (es) * | 2006-06-09 | 2009-01-09 | Wellstat Therapeutics Corp | Compuestos para el tratamiento de trastornos metabolicos. |
NZ574664A (en) * | 2006-08-17 | 2012-06-29 | Wellstat Therapeutics Corp | Combination treatment for metabolic disorders comprising an incretin mimetic such as exendin or a dppv iv inhibitor |
WO2008030752A2 (en) * | 2006-09-07 | 2008-03-13 | N.V. Organon | Methods for determining effective doses of fatty acid amide hydrolase inhibitors in vivo |
US20090099240A1 (en) * | 2006-10-02 | 2009-04-16 | N.V. Organon | Methods for treating energy metabolism disorders by inhibiting fatty acid amide hydrolase activity |
WO2008063714A1 (en) * | 2006-11-20 | 2008-05-29 | N.V. Organon | Metabolically-stabilized inhibitors of fatty acid amide hydrolase |
KR20090094125A (ko) | 2006-12-08 | 2009-09-03 | 엑셀리시스, 인코포레이티드 | Lxr 및 fxr 조절자 |
PE20090159A1 (es) * | 2007-03-08 | 2009-02-21 | Plexxikon Inc | COMPUESTOS DERIVADOS DE ACIDO INDOL-PROPIONICO COMO MODULADORES PPARs |
US20160331729A9 (en) | 2007-04-11 | 2016-11-17 | Omeros Corporation | Compositions and methods for prophylaxis and treatment of addictions |
EP3788877A1 (en) * | 2007-04-11 | 2021-03-10 | Omeros Corporation | Compositions and methods for prophylaxis and treatment of addictions |
US11241420B2 (en) | 2007-04-11 | 2022-02-08 | Omeros Corporation | Compositions and methods for prophylaxis and treatment of addictions |
EP2240024A4 (en) * | 2008-01-15 | 2014-05-21 | Wellstat Therapeutics Corp | COMPOUNDS FOR THE TREATMENT OF METABOLIC DISORDERS |
US8470337B2 (en) * | 2008-03-13 | 2013-06-25 | Allergan, Inc. | Therapeutic treatments using botulinum neurotoxin |
UA103894C2 (ru) | 2008-03-13 | 2013-12-10 | Уеллстат Терепьютикс Корпорейшн | Соединения и способ для снижения уровня мочевой кислоты |
KR101037178B1 (ko) * | 2008-04-10 | 2011-05-26 | 건국대학교 산학협력단 | 비뉴클레오시드 계열의 c형 간염 치료 또는 예방제 |
EP2282736B1 (en) | 2008-04-30 | 2015-11-11 | Wellstat Therapeutics Corporation | Tetrazole compounds for reducing uric acid |
US8664433B2 (en) * | 2008-05-05 | 2014-03-04 | Wellstat Therapeutics Corporation | Synthesis of 4-[3-(2,6-dimethylbenzyloxy)phenyl]-4-oxobutanoic acid |
US8703991B2 (en) | 2008-11-04 | 2014-04-22 | Wellstat Therapeutics Corporation | Synthesis of (phenylalkyloxy)phenyl-oxobutanoic acids |
KR20120039742A (ko) | 2009-07-31 | 2012-04-25 | 가부시끼가이샤 스텔릭 사이세이 이카가꾸 겐뀨쇼 | 지방성 간염-간암 모델 동물 |
EP2488020B1 (en) | 2009-10-13 | 2016-12-14 | Wellstat Therapeutics Corporation | 3-substituted compounds for reducing uric acid |
WO2012033720A1 (en) | 2010-09-08 | 2012-03-15 | Wellstat Therapeutics Corporation | Benzoic acid compounds for reducing uric acid |
US20140107166A1 (en) * | 2011-02-14 | 2014-04-17 | Dana-Farber Cancer Institute, Inc. | Histone deacetylase inhibitors and methods of use thereof |
FR2974065B1 (fr) * | 2011-04-14 | 2013-05-10 | Snecma | Procede de montage d'un moteur d'aeronef sur un pylone et attache moteur pour la mise en oeuvre d'un tel procede. |
FR2976943B1 (fr) * | 2011-06-23 | 2013-07-12 | Metabolys | Derives de piperazine, leurs procedes de preparation et leurs utilisations dans le traitement de l'insulinoresistance |
FR2976942B1 (fr) | 2011-06-23 | 2013-07-12 | Metabolys | Derives de piperazine, leurs procedes de preparation et leurs utilisations dans le traitement de l'insulinoresistance |
FR2999427B1 (fr) | 2012-12-17 | 2015-01-30 | Metabolys | Composition et kit comprenant des derives de piperazine et de la metformine, leur utilisation dans le traitement du diabete |
WO2015086490A1 (de) * | 2013-12-11 | 2015-06-18 | Bayer Cropscience Ag | Verfahren zur herstellung von halogenierten di-substituierten benzylaminen, insbesondere halogenierten dialkylbenzylaminen |
US20190038650A1 (en) * | 2016-02-01 | 2019-02-07 | Babak Razani | Compositions and methods for the treatment of atherosclerosis and hepatosteatosis and other diseases |
EP3278802A1 (en) * | 2016-08-04 | 2018-02-07 | Metabolys | New treatment for the non alcoholic steatohepatitis and fibrosis |
CN108610285B (zh) * | 2017-03-17 | 2020-04-28 | 上海柏翱纳吉医药科技有限公司 | 苯乙酮类化合物、其制备方法及其在防治脂肪肝方面的应用 |
WO2019224393A1 (en) * | 2018-05-25 | 2019-11-28 | University Of Copenhagen | Fenofibrate for reducing hypoglycemia in type 1 diabetes/lada |
BR112021006907A2 (pt) * | 2018-10-11 | 2021-09-08 | Basf As | Compostos aromáticos e usos farmacêuticos destes |
CN113134086A (zh) * | 2020-01-20 | 2021-07-20 | 深圳市长卿医学研究院 | 一种降血脂的药物组合物 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2309986A1 (de) * | 1973-02-28 | 1974-08-29 | Menarini Sas | N-(o-hydroxybenzoyl)-p-(2-dialkylaminoaethoxy)-phenylamine sowie osubstituierte derivate und quartaere salze derselben |
US4098816A (en) * | 1973-08-23 | 1978-07-04 | Beecham Group Limited | Polycyclic oxy-aromatic acid |
WO1999011255A1 (fr) * | 1997-08-28 | 1999-03-11 | Ono Pharmaceutical Co., Ltd. | Regulateurs du recepteur active par les agents de proliferation des peroxysomes |
WO1999020275A1 (en) * | 1997-10-17 | 1999-04-29 | Aventis Pharmaceuticals Products Inc. | Therapeutic uses of quinoline derivatives |
WO2001040170A1 (en) * | 1999-12-03 | 2001-06-07 | Astrazeneca Ab | New phenalkyloxy-phenyl derivatives |
Family Cites Families (134)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR5035E (fr) | 1902-08-29 | 1905-12-02 | Paul Wilhelm Sieurin | Engin à puiser à fond de cale des navires et à élever des matières |
GB148830A (en) | 1918-12-04 | 1921-11-10 | Aegir Electrische Bordapp Und | Device for signalling liquid levels at a distance |
FR5035M (zh) * | 1964-07-28 | 1967-05-02 | ||
CH560193A5 (zh) | 1968-06-14 | 1975-03-27 | Ciba Geigy Ag | |
JPS4725149U (zh) | 1971-04-14 | 1972-11-21 | ||
BE787782A (fr) * | 1971-08-20 | 1973-02-19 | Thomae Gmbh Dr K | Nouveaux 4-(4-biphenylyl)-butyramides |
GB1437781A (en) * | 1972-04-04 | 1976-06-03 | Beecham Group Ltd | Pyridine derivatives having hypoglycaemic activity |
FR2191887A1 (en) | 1972-07-07 | 1974-02-08 | Ugine Kuhlmann | 7-Substd 5-hydroxy-imidazo pyrimidines - antiinflammatories, and immuno-suppressives, from 2-aminoimidazoline and substd ethyl acetates |
DE2252818A1 (de) * | 1972-10-27 | 1974-05-09 | Nippon Soda Co | Aralkylarylaether oder -thioaether und ihre verwendung als regulatoren fuer das pflanzenwachstum |
NL7307100A (en) | 1973-05-22 | 1974-11-26 | 1,3-dimethylpyrogallol derivs pharmaceutical inters - prepd. from (3,5-dimethoxy-benzyloxybenzoyl)acetic acid methyl ester and sulphurylchloride | |
GB1482195A (en) * | 1973-08-23 | 1977-08-10 | Beecham Group Ltd | Biologically active phenyl(thio)ether derivatives |
US4011321A (en) | 1973-12-19 | 1977-03-08 | Smith Kline & French Laboratories Limited | Pharmaceutical compositions and methods of inhibiting β-adrenergic receptors |
GB1488330A (en) | 1973-12-19 | 1977-10-12 | Smith Kline French Lab | Dihydropyridazinones |
JPS5811874B2 (ja) | 1974-03-25 | 1983-03-04 | 武田薬品工業株式会社 | ピリド (3,4−d) ピリダジンルイノ セイゾウホウ |
IE42214B1 (en) | 1974-06-18 | 1980-07-02 | Smith Kline French Lab | Hydrazinopyredazines |
GB1479759A (en) * | 1974-11-23 | 1977-07-13 | Lepetit Spa | Heterocyclic fused derivatives of indole and quinoline |
JPS5225734A (en) | 1975-08-23 | 1977-02-25 | Kyorin Pharmaceut Co Ltd | Process for preparation of 4-(4'-halogenobenzyloxy)-bonzoyl acetate |
JPS5515460A (en) * | 1978-07-20 | 1980-02-02 | Hisamitsu Pharmaceut Co Inc | Novel 2-substituted-benzoylpropionic acid derivative |
US4268442A (en) * | 1978-11-14 | 1981-05-19 | Sagami Chemical Research Center | Process for preparing aromatic acetic acid |
JPS56115747A (en) | 1980-02-19 | 1981-09-11 | Nippon Synthetic Chem Ind Co Ltd:The | 2- 2-hydroxyethylamino -3-substituted benzoylpropionic acid, its preparation and germicide |
DE3012012A1 (de) | 1980-03-28 | 1981-10-08 | Beiersdorf Ag, 2000 Hamburg | Substituierte 3-aryl-2-cycloalken-1-one und verfahren zu ihrer herstellung |
ZA825227B (en) | 1981-07-22 | 1984-03-28 | Syntex Inc | Substituted pyrrolidine cardiovascular system regulators antihypertensives |
IT1171604B (it) | 1981-10-22 | 1987-06-10 | Roussel Maestretti Spa | Derivati di acido 4-fenil-4-ossobuten-2-oico dotati di proprieta' farmacologiche e loro procedimento di preparazione |
EP0101223B1 (en) * | 1982-08-06 | 1987-04-01 | Ube Industries, Ltd. | process for producing phenylacetones |
US4474809A (en) * | 1983-01-20 | 1984-10-02 | American Cyanamid Company | Arylglyoxals |
JPS6140270A (ja) | 1984-08-01 | 1986-02-26 | Morishita Seiyaku Kk | ピリダジノン誘導体 |
US4874777A (en) | 1987-04-10 | 1989-10-17 | Eli Lilly And Company | Leukotriene antagonists |
JPS63270661A (ja) | 1987-04-28 | 1988-11-08 | Taki Chem Co Ltd | 1−〔2−(4−ヒドロキシベンゾイル)エタノイル〕−2−ピペリドン及びその製造法並びにそれを有効成分とするアルコ−ル発酵促進剤 |
DE3720317A1 (de) * | 1987-06-19 | 1988-12-29 | Sandoz Ag | Neue allylaminderivate |
JPS6438636A (en) * | 1987-08-05 | 1989-02-08 | Ajinomoto Kk | Fluorescent analyzer |
JPS6463570A (en) | 1987-09-03 | 1989-03-09 | Taki Chemical | 1-(3-(4-hydroxyphenyl)-3-hydroxypropanoyl)-2-piperidone, its production and plant growth regulator therefrom |
JP2534744B2 (ja) | 1988-01-13 | 1996-09-18 | 株式会社リコー | カラ―画像符号化方式 |
US4845231A (en) | 1988-02-12 | 1989-07-04 | American Home Products Corporation | Tetrazoles and their use as hypoglycemic agents |
GB8804457D0 (en) | 1988-02-25 | 1988-03-23 | Ciba Geigy Ag | Compositions |
JPH01216961A (ja) * | 1988-02-25 | 1989-08-30 | Takeda Chem Ind Ltd | 12−リポキシゲネース阻害剤 |
CA2012681A1 (en) | 1989-03-31 | 1990-09-30 | Masayasu Okuhira | Quinolone derivatives, preparation processes thereof, and antibacterial agents containing the same |
US4895862A (en) * | 1989-04-21 | 1990-01-23 | American Home Products Corp. | Novel benzyl-3H-1,2,3,5-oxathiadiazole 2-oxides useful as antihyperglycemic agents |
US4911555A (en) * | 1989-05-04 | 1990-03-27 | The Jackson Laboratory | Magnetic stirrer for multiple samples |
DE3923093A1 (de) | 1989-07-13 | 1991-01-24 | Basf Ag | Neue 3-methoximinopropionsaeureester und diese enthaltende fungizide |
JPH0348603A (ja) * | 1989-07-14 | 1991-03-01 | Wakayama Pref Gov | 抗菌防臭材料 |
WO1991007502A1 (en) * | 1989-11-08 | 1991-05-30 | Baylor College Of Medicine | Methods and reagents to detect and characterize norwalk and related viruses |
US6572862B1 (en) * | 1989-11-08 | 2003-06-03 | Baylor College Of Medicine | Methods and reagents to detect and characterize Norwalk and related viruses |
CA2029219A1 (en) * | 1989-11-08 | 1991-05-09 | Mary K. Estes | Methods and reagents to detect and characterize norwalk and related viruses |
US5149737A (en) * | 1990-06-18 | 1992-09-22 | Eastman Kodak Company | Carboxy containing monomers and polymers and latices prepared from same |
DE69113874T2 (de) * | 1990-06-21 | 1996-03-28 | Zeneca Ltd | Zyklische Ether-Derivate. |
AU638840B2 (en) * | 1990-07-05 | 1993-07-08 | Sumitomo Chemical Company, Limited | Pyrimidine derivative |
JPH0495049A (ja) * | 1990-08-08 | 1992-03-27 | Asahi Chem Ind Co Ltd | ビフェニル‐5,5’‐ビス‐アルカン酸誘導体、その製造法およびその用途 |
JPH04159266A (ja) * | 1990-10-19 | 1992-06-02 | Fujisawa Pharmaceut Co Ltd | ピリミジノン誘導体 |
ES2094344T3 (es) | 1991-01-02 | 1997-01-16 | Merrell Pharma Inc | Compuestos anti-virales. |
NL9100770A (nl) * | 1991-05-03 | 1992-12-01 | Hubertine Maria Emilie Aalders | Opslagdoos voor een bril en contactlenzen. |
TW201311B (zh) * | 1991-06-17 | 1993-03-01 | Hoffmann La Roche | |
AU669866B2 (en) | 1991-11-05 | 1996-06-27 | Smithkline Beecham Corporation | Endothelin receptor antagonists |
US5817693A (en) * | 1991-11-05 | 1998-10-06 | Cousins; Russell Donovan | Endothelin receptor antagonists |
JPH05230009A (ja) * | 1992-02-24 | 1993-09-07 | Taisho Pharmaceut Co Ltd | アミジン誘導体 |
US5648368A (en) * | 1992-12-01 | 1997-07-15 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
TW273551B (zh) | 1993-05-24 | 1996-04-01 | Wakiei Seiyaku Kk | |
US5591862A (en) * | 1993-06-11 | 1997-01-07 | Takeda Chemical Industries, Ltd. | Tetrazole derivatives, their production and use |
IT1265101B1 (it) * | 1993-07-23 | 1996-10-30 | Erba Carlo Spa | Derivati dell'acido 2-ammino-4-fenil-4-osso butirrico |
SK20396A3 (en) * | 1993-08-19 | 1997-03-05 | Warner Lambert Co | Substituted 2(5h)furanone, 2(5h)thiophenone or 2(5h)pyrrolone derivatives and pharmaceutical compositions on their base |
IL111613A0 (en) | 1993-11-12 | 1995-01-24 | Rhone Poulenc Rorer Ltd | Substituted phenyl compounds, their preparation and pharmaceutical compositions containing them |
US5665387A (en) * | 1994-09-01 | 1997-09-09 | K.U. Leuven Research & Development | Methods and compositions for primary and secondary prevention of autoimmune diabetes |
US5641796A (en) * | 1994-11-01 | 1997-06-24 | Eli Lilly And Company | Oral hypoglycemic agents |
US5975711A (en) * | 1995-06-27 | 1999-11-02 | Lumitex, Inc. | Integrated display panel assemblies |
US20020058931A1 (en) * | 1995-06-27 | 2002-05-16 | Jeffrey R. Parker | Light delivery system and applications thereof |
US5613751A (en) * | 1995-06-27 | 1997-03-25 | Lumitex, Inc. | Light emitting panel assemblies |
US7108414B2 (en) * | 1995-06-27 | 2006-09-19 | Solid State Opto Limited | Light emitting panel assemblies |
US6185356B1 (en) * | 1995-06-27 | 2001-02-06 | Lumitex, Inc. | Protective cover for a lighting device |
US6712481B2 (en) * | 1995-06-27 | 2004-03-30 | Solid State Opto Limited | Light emitting panel assemblies |
US20040135273A1 (en) * | 1995-06-27 | 2004-07-15 | Parker Jeffery R. | Methods of making a pattern of optical element shapes on a roll for use in making optical elements on or in substrates |
CA2234633A1 (en) | 1995-10-17 | 1997-04-24 | G.D. Searle & Co. | Method of detecting cyclooxygenase-2 |
GB9521486D0 (en) * | 1995-10-20 | 1995-12-20 | Pharmacia Spa | Fluoro-substituted benzoylpropionic acid derivatives |
GB9522615D0 (en) * | 1995-11-03 | 1996-01-03 | Pharmacia Spa | 4-Phenyl-4-oxo-butanoic acid derivatives with kynurenine-3-hydroxylase inhibiting activity |
GB9522617D0 (en) * | 1995-11-03 | 1996-01-03 | Pharmacia Spa | 4-Phenyl-4-oxo-butenoic acid derivatives with kynurenine-3-hydroxylase inhibiting activity |
JP3906935B2 (ja) | 1995-12-18 | 2007-04-18 | 杏林製薬株式会社 | N−置換ジオキソチアゾリジルベンズアミド誘導体及びその製造法 |
AU719396B2 (en) | 1996-02-19 | 2000-05-11 | Japan Tobacco Inc. | Therapeutic agent for diabetes |
EP0912562A1 (en) | 1996-07-19 | 1999-05-06 | Takeda Chemical Industries, Ltd. | Heterocyclic compounds, their production and use |
FR2752422B1 (fr) | 1996-08-16 | 1998-11-06 | Lipha | Composition pharmaceutique contenant des acides 4-oxo-butanoiques |
KR100205768B1 (en) * | 1996-08-24 | 1999-07-01 | Choongwae Pharm Co | Stereo-selective composition of 4-acetoxyazetidinone |
AU3867997A (en) | 1996-08-27 | 1998-03-19 | Shionogi & Co., Ltd. | Chromene-3-carboxylate derivatives |
EP0927035A4 (en) * | 1996-09-13 | 2002-11-13 | Merck & Co Inc | THROMBIN INHIBITORS |
US6121251A (en) * | 1996-10-11 | 2000-09-19 | Rohm And Haas Company | Dihydropyridazinones and pyridazinones and their use as fungicides and insecticides |
JPH10130241A (ja) | 1996-10-31 | 1998-05-19 | Wakunaga Pharmaceut Co Ltd | 新規ピリドンカルボン酸誘導体又はその塩及びこれを含有する医薬 |
MXPA99001974A (es) | 1996-12-09 | 2002-03-27 | Warner Lambert Co | Metodo para tratar y prevenir fallas cardiacas y dilatacion ventricular. |
IT1289238B1 (it) | 1996-12-10 | 1998-09-29 | Bio S S P A Ora Bio S S R L | Composizioni farmaceutiche per il trattamento di infezioni virali comprendenti una 4 arilcumarina |
US6038332A (en) | 1997-09-05 | 2000-03-14 | Digital Biometrics, Inc. | Method and apparatus for capturing the image of a palm |
US6376546B1 (en) | 1997-10-14 | 2002-04-23 | Asahi Kasei Kabushiki Kaisha | Biphenyl-5-alkanoic acid derivatives and use thereof |
JP3608929B2 (ja) | 1997-12-19 | 2005-01-12 | セントラル硝子株式会社 | ポリイミド組成物 |
ATE451346T1 (de) * | 1998-03-10 | 2009-12-15 | Ono Pharmaceutical Co | Carbonsäurederivate und medikamente die diese als aktiven wirkstoff enthalten |
BR9802163A (pt) | 1998-05-29 | 2000-11-28 | Ind E Com De Prod Farmaceutico | Composiçoes farmacêuticas para o tratamento de infecções virais compreendendo substâncias neoflavonoides (4-arilcumarinas) |
WO1999062520A1 (en) | 1998-06-03 | 1999-12-09 | Merck & Co., Inc. | Hiv integrase inhibitors |
SE9801992D0 (sv) | 1998-06-04 | 1998-06-04 | Astra Ab | New 3-aryl-2-hydroxypropionic acid derivative I |
EP1085846A2 (en) * | 1998-06-08 | 2001-03-28 | Advanced Medicine, Inc. | Multibinding inhibitors of microsomal triglyceride transferase protein |
WO2000006996A1 (en) * | 1998-07-28 | 2000-02-10 | Ce Resources Pte Ltd. | Optical detection system |
PT997474E (pt) * | 1998-08-14 | 2004-01-30 | Pfizer | Agentes antitromboticos |
US6255498B1 (en) | 1998-10-16 | 2001-07-03 | Millennium Pharmaceuticals, Inc. | Method for synthesizing diaryl-substituted heterocyclic compounds, including tetrahydrofurans |
US6291503B1 (en) * | 1999-01-15 | 2001-09-18 | Bayer Aktiengesellschaft | β-phenylalanine derivatives as integrin antagonists |
US6613513B1 (en) * | 1999-02-23 | 2003-09-02 | Caliper Technologies Corp. | Sequencing by incorporation |
US6827456B2 (en) * | 1999-02-23 | 2004-12-07 | Solid State Opto Limited | Transreflectors, transreflector systems and displays and methods of making transreflectors |
US6752505B2 (en) * | 1999-02-23 | 2004-06-22 | Solid State Opto Limited | Light redirecting films and film systems |
US7364341B2 (en) * | 1999-02-23 | 2008-04-29 | Solid State Opto Limited | Light redirecting films including non-interlockable optical elements |
US20050024849A1 (en) * | 1999-02-23 | 2005-02-03 | Parker Jeffery R. | Methods of cutting or forming cavities in a substrate for use in making optical films, components or wave guides |
JP2002542224A (ja) | 1999-04-19 | 2002-12-10 | コーエラカント コーポレイション | Ii型糖尿病の治療薬としてのppar−(ガンマ)作用物質 |
DE60042738D1 (de) * | 1999-05-07 | 2009-09-24 | Life Technologies Corp | Verfahren zum nachweis von analyten mit hilfe von halbleiternanokrystallen |
DE29923419U1 (de) | 1999-07-01 | 2001-02-08 | Asta Medica Ag | Neue Xanthonverbindungen und diese enthaltende Arzneimittel |
US6541521B1 (en) | 1999-07-12 | 2003-04-01 | Warner-Lambert Company | Benzene butyric acids and their derivatives as inhibitors of matrix metalloproteinases |
US20030092058A1 (en) * | 1999-08-10 | 2003-05-15 | Spaulding Glenn F. | Novel flow cytometer |
US6706763B1 (en) * | 1999-09-17 | 2004-03-16 | Kyorin Pharmaceutical Co., Ltd. | O-anisamide derivatives |
JP2001181281A (ja) | 1999-10-12 | 2001-07-03 | Sato Pharmaceutical Co Ltd | 抗菌剤として有用なキノロン誘導体 |
US6677473B1 (en) | 1999-11-19 | 2004-01-13 | Corvas International Inc | Plasminogen activator inhibitor antagonists |
US6610351B2 (en) * | 2000-04-12 | 2003-08-26 | Quantag Systems, Inc. | Raman-active taggants and their recognition |
EP1276739A2 (en) | 2000-04-24 | 2003-01-22 | Bristol-Myers Squibb Company | Heterocycles that are inhibitors of impdh enzyme |
AU6118001A (en) | 2000-05-03 | 2001-11-12 | Tularik Inc | Combination therapeutic compositions and methods of use |
ES2288957T3 (es) | 2000-05-12 | 2008-02-01 | Ortho-Mcneil Pharmaceutical, Inc. | 4h-benzo(1.4)oxazin-3-ina biologicamente activas. |
WO2002002119A1 (en) | 2000-06-29 | 2002-01-10 | Smithkline Beecham Corporation | Fatty acid synthase inhibitors |
EP1300142A4 (en) | 2000-07-05 | 2004-05-19 | Ajinomoto Kk | HYPOGLYCEMIC COMPOUNDS |
US7354954B1 (en) * | 2000-08-10 | 2008-04-08 | Meythaler Jay M | Use of GABA agonists for treatment of spastic disorders, convulsions, and epilepsy |
EP1310494B1 (en) | 2000-08-11 | 2012-01-25 | Nippon Chemiphar Co., Ltd. | PPAR (delta) ACTIVATORS |
US6982348B2 (en) | 2001-01-26 | 2006-01-03 | Takeda Pharmaceutical Company Limited | Aminoethanol derivatives |
EE200400001A (et) | 2001-06-07 | 2004-02-16 | Eli Lilly And Company | alfa-metoksütsinnamaadid, nende valmistamine ja kasutamine peroksisoomi proliferaator-aktiveeritud retseptorite moduleerimiseks ning neid sisaldavad ravimkompositsioonid |
MXPA03011558A (es) | 2001-06-12 | 2004-03-26 | Wellstat Therapeutics Corp | Compuestos para el tratamiento de desordenes metabolicos. |
DE10135027A1 (de) | 2001-07-18 | 2003-02-06 | Solvay Pharm Gmbh | Verwendung Trifluoracetylalkyl-substituierter Phenyl-, Phenol- und Benzoylderivate in der Behandlung und/oder Prophylaxe von Obestias und deren Begleit- und/oder Folgeerkrankungen |
JP2003248008A (ja) * | 2001-12-18 | 2003-09-05 | Inst Of Physical & Chemical Res | 反応液の攪拌方法 |
US7645772B2 (en) | 2002-11-01 | 2010-01-12 | Wellstat Therapeutics Corporation | Treatment of metabolic disorders |
US7615575B2 (en) | 2003-02-13 | 2009-11-10 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
SI1633340T1 (sl) * | 2003-04-15 | 2011-02-28 | Wellstat Therapeutics Corp | Spojine za zdravljenje metaboličnih motenj |
JP4697973B2 (ja) * | 2003-04-22 | 2011-06-08 | ウェルスタット セラピューティクス コーポレイション | 代謝障害の処置のための化合物 |
WO2004098496A2 (en) | 2003-04-30 | 2004-11-18 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
GB0314078D0 (en) | 2003-06-18 | 2003-07-23 | Astrazeneca Ab | Therapeutic agents |
WO2005019151A1 (en) | 2003-08-20 | 2005-03-03 | Eli Lilly And Company | Ppar modulators |
US20050262567A1 (en) * | 2004-05-19 | 2005-11-24 | Itshak Carmona | Systems and methods for computer security |
US7319522B2 (en) * | 2004-05-27 | 2008-01-15 | Finesse Solutions Llc. | Systems and methods for in situ spectroscopic measurements |
EP1846751B1 (en) * | 2005-01-31 | 2020-04-22 | The Board of Trustees of the University of Illionis | Methods and devices for characterizing particles in clear and turbid media |
US8022249B2 (en) | 2005-04-01 | 2011-09-20 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
AU2007235145B2 (en) * | 2006-03-31 | 2011-09-22 | Wellstat Therapeutics Corporation | Combination treatment of metabolic disorders |
-
2002
- 2002-06-12 MX MXPA03011558A patent/MXPA03011558A/es active IP Right Grant
- 2002-06-12 UA UAA200709376A patent/UA104987C2/uk unknown
- 2002-06-12 CA CA2450221A patent/CA2450221C/en not_active Expired - Fee Related
- 2002-06-12 CN CNB028118812A patent/CN100344616C/zh not_active Expired - Fee Related
- 2002-06-12 CN CN2011100531191A patent/CN102140064A/zh active Pending
- 2002-06-12 KR KR1020097009825A patent/KR100965201B1/ko not_active IP Right Cessation
- 2002-06-12 KR KR1020107021892A patent/KR101059776B1/ko not_active IP Right Cessation
- 2002-06-12 CN CN2011100525843A patent/CN102151262A/zh active Pending
- 2002-06-12 US US10/481,042 patent/US7329782B2/en not_active Expired - Fee Related
- 2002-06-12 WO PCT/US2002/018388 patent/WO2002100341A2/en active Application Filing
- 2002-06-12 JP JP2003503168A patent/JP4711621B2/ja not_active Expired - Lifetime
- 2002-06-12 US US10/167,839 patent/US7101910B2/en not_active Expired - Lifetime
- 2002-06-12 RU RU2004100306/04A patent/RU2341513C2/ru not_active IP Right Cessation
- 2002-06-12 EP EP02744271.4A patent/EP1461323B1/en not_active Expired - Lifetime
- 2002-06-12 KR KR1020107003045A patent/KR101009472B1/ko not_active IP Right Cessation
- 2002-06-12 CN CN2007101492677A patent/CN101444496B/zh not_active Expired - Fee Related
- 2002-06-12 CZ CZ20033394A patent/CZ20033394A3/cs unknown
- 2002-06-12 HU HU0600781A patent/HU230352B1/hu not_active IP Right Cessation
- 2002-06-12 KR KR1020037016340A patent/KR100959356B1/ko not_active IP Right Cessation
- 2002-06-12 BR BRPI0210383-4A patent/BRPI0210383B1/pt not_active IP Right Cessation
- 2002-06-12 ES ES02744271.4T patent/ES2441874T3/es not_active Expired - Lifetime
- 2002-06-12 AU AU2002345625A patent/AU2002345625B2/en not_active Ceased
- 2002-06-12 IL IL15932002A patent/IL159320A0/xx unknown
- 2002-06-12 NZ NZ530051A patent/NZ530051A/en not_active IP Right Cessation
- 2002-12-06 UA UA20031211545A patent/UA82831C2/uk unknown
-
2003
- 2003-10-14 US US10/685,183 patent/US6946491B2/en not_active Expired - Lifetime
- 2003-10-14 US US10/684,644 patent/US6924314B2/en not_active Expired - Fee Related
- 2003-10-14 US US10/684,740 patent/US7045541B2/en not_active Expired - Fee Related
- 2003-10-14 US US10/684,730 patent/US6916848B2/en not_active Expired - Fee Related
- 2003-10-14 US US10/684,735 patent/US7041659B2/en not_active Expired - Lifetime
- 2003-10-14 US US10/684,660 patent/US6858602B2/en not_active Expired - Fee Related
- 2003-12-11 NO NO20035526A patent/NO333355B1/no not_active IP Right Cessation
- 2003-12-11 ZA ZA2003/09627A patent/ZA200309627B/en unknown
- 2003-12-11 IL IL159320A patent/IL159320A/en not_active IP Right Cessation
-
2004
- 2004-06-10 US US10/865,088 patent/US20040242692A1/en not_active Abandoned
- 2004-07-16 US US10/892,950 patent/US7012071B2/en not_active Expired - Fee Related
- 2004-12-06 US US11/005,449 patent/US8487000B2/en not_active Expired - Fee Related
-
2005
- 2005-09-30 HK HK05108684A patent/HK1076805A1/xx not_active IP Right Cessation
-
2006
- 2006-09-27 US US11/535,779 patent/US8552062B2/en not_active Expired - Fee Related
-
2007
- 2007-06-28 AU AU2007203009A patent/AU2007203009B2/en not_active Ceased
- 2007-07-02 US US11/772,515 patent/US20070244171A1/en not_active Abandoned
- 2007-07-02 US US11/772,501 patent/US20070249696A1/en not_active Abandoned
- 2007-07-02 US US11/772,556 patent/US20070265323A1/en not_active Abandoned
- 2007-07-02 US US11/772,560 patent/US8604083B2/en not_active Expired - Fee Related
- 2007-07-02 US US11/772,520 patent/US20070244141A1/en not_active Abandoned
- 2007-07-02 US US11/772,511 patent/US20070249719A1/en not_active Abandoned
- 2007-07-02 US US11/772,504 patent/US7851494B2/en not_active Expired - Fee Related
- 2007-08-20 US US11/841,508 patent/US20080015209A1/en not_active Abandoned
- 2007-08-24 US US11/844,431 patent/US7547802B2/en not_active Expired - Fee Related
- 2007-08-24 US US11/844,432 patent/US7863475B2/en not_active Expired - Fee Related
-
2008
- 2008-08-04 RU RU2008132204/04A patent/RU2502723C2/ru not_active IP Right Cessation
-
2009
- 2009-07-07 JP JP2009161270A patent/JP2009221232A/ja active Pending
- 2009-07-07 JP JP2009161269A patent/JP5477893B2/ja not_active Expired - Fee Related
- 2009-07-23 HK HK09106761.5A patent/HK1126987A1/xx not_active IP Right Cessation
-
2010
- 2010-12-08 IL IL209842A patent/IL209842A0/en unknown
-
2011
- 2011-03-08 AU AU2011201016A patent/AU2011201016B2/en not_active Ceased
-
2012
- 2012-04-24 IL IL219397A patent/IL219397A/en not_active IP Right Cessation
- 2012-04-24 IL IL219396A patent/IL219396A0/en unknown
-
2013
- 2013-02-08 NO NO20130218A patent/NO20130218L/no not_active Application Discontinuation
- 2013-03-06 JP JP2013043951A patent/JP2013129665A/ja not_active Withdrawn
- 2013-06-18 US US13/920,579 patent/US9133073B2/en not_active Expired - Fee Related
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2309986A1 (de) * | 1973-02-28 | 1974-08-29 | Menarini Sas | N-(o-hydroxybenzoyl)-p-(2-dialkylaminoaethoxy)-phenylamine sowie osubstituierte derivate und quartaere salze derselben |
US4098816A (en) * | 1973-08-23 | 1978-07-04 | Beecham Group Limited | Polycyclic oxy-aromatic acid |
WO1999011255A1 (fr) * | 1997-08-28 | 1999-03-11 | Ono Pharmaceutical Co., Ltd. | Regulateurs du recepteur active par les agents de proliferation des peroxysomes |
WO1999020275A1 (en) * | 1997-10-17 | 1999-04-29 | Aventis Pharmaceuticals Products Inc. | Therapeutic uses of quinoline derivatives |
WO2001040170A1 (en) * | 1999-12-03 | 2001-06-07 | Astrazeneca Ab | New phenalkyloxy-phenyl derivatives |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN100344616C (zh) | 用于治疗代谢失调的化合物 | |
CN1190434C (zh) | 新的杂环化合物、其制备方法和含有它们的药物组合物及其在治疗糖尿病和相关疾病中的应用 | |
CN1259307C (zh) | 酰化的二氢化茚基胺及其作为药物的用途 | |
CN1228327C (zh) | 羧酸衍生物和包含它们的药物 | |
CN1040433C (zh) | 唑类化合物及其生产方法和应用 | |
CN1578659A (zh) | 过氧化物酶体增殖剂激活的受体(ppar)的调节剂 | |
CN101031540A (zh) | 六氟异丙醇取代的醚衍生物 | |
CN1750758A (zh) | 用于治疗代谢紊乱的化合物 | |
CN1714079A (zh) | 扁桃酸衍生物 | |
CN101048402A (zh) | 咔唑衍生物、其溶剂合物或其药学上允许的盐 | |
CN1479728A (zh) | 过氧化物酶体增殖子激活受体α激动剂 | |
CN1909902A (zh) | 用于治疗糖尿病的作为ppar调节剂的三唑、噁二唑和噻二唑衍生物 | |
CN1069727A (zh) | 用于治疗的酰胺 | |
CN1351597A (zh) | 抗糖尿病的新型多晶形物、其制备方法和含有它们的药物组合物 | |
CN1751038A (zh) | 作为葡萄糖代谢调节剂的经取代芳基和杂芳基衍生物及葡萄糖代谢失调的预防和治疗 | |
CN1527822A (zh) | 用于治疗与paar有关的疾病的噻唑衍生物 | |
CN1378537A (zh) | 嘧啶衍生物 | |
CN1311767A (zh) | 治疗代谢性疾病的糖皮质激素和甲状腺激素受体的配体 | |
CN1697828A (zh) | 新颖的化合物和它们在医药中的用途、它们的制备方法与含有它们的药物组合物 | |
CN1774244A (zh) | 用于治疗代谢紊乱的化合物 | |
CN1257886C (zh) | 脱氢氨基酸类化合物 | |
CN1780614A (zh) | 用于治疗代谢紊乱的化合物 | |
CN1751037A (zh) | 作为ppar调节剂的磺酰胺衍生物 | |
CN1083481A (zh) | 4,1-苯并氧氮杂䓬衍生物和其用途 | |
CN1212861C (zh) | 以NF-κB抑制剂为有效成分的心肌炎、扩张型心肌病和心衰的预防或治疗药 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CI01 | Publication of corrected invention patent application |
Correction item: Inventor Correct: Sullivan Sharma|Bobst Reed W. von|Kevin L. Hodge|Michael K. Barnett|Steven D. Wopa False: Sullivan Sharma|Bobst Reed W. von|Kevin L. Hodge|Michael K. Barnett Number: 16 Page: 261 Volume: 21 |
|
CI02 | Correction of invention patent application |
Correction item: Inventor Correct: Sullivan Sharma|Bobst Reed W. von|Kevin L. Hodge|Michael K. Barnett|Steven D. Wopa False: Sullivan Sharma|Bobst Reed W. von|Kevin L. Hodge|Michael K. Barnett Number: 16 Page: The title page Volume: 21 |
|
COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: HODGE KIRVIN L. REID W FENG BOSHITEER BORSTEL REID W. VON MICHAEL K BANATE TO: HODGE KIRVIN L. REID W FENG BOSHITEER BORSTEL REID W. VON MICHAEL K BANATE STEPHEN D WOPA |
|
ERR | Gazette correction |
Free format text: CORRECT: INVENTOR; FROM: HODGE KIRVIN L. REID W FENG BOSHITEER BORSTEL REID W. VON MICHAEL K BANATE TO: HODGE KIRVIN L. REID W FENG BOSHITEER BORSTEL REID W. VON MICHAEL K BANATE STEPHEN D WOPA |
|
CI01 | Publication of corrected invention patent application |
Correction item: Inventor Correct: Wolpe Stephen D. False: There are fifth inventors missing Number: 16 Volume: 21 |
|
CI02 | Correction of invention patent application |
Correction item: Inventor Correct: Wolpe Stephen D. False: There are fifth inventors missing Number: 16 Page: The title page Volume: 21 |
|
ERR | Gazette correction |
Free format text: CORRECT: INVENTOR; FROM: LACK INVENTION OF THE FIRST FIVE PEOPLE TO: STEPHEN D WOPA |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1076805 Country of ref document: HK |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1076805 Country of ref document: HK |
|
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20071024 Termination date: 20170612 |
|
CF01 | Termination of patent right due to non-payment of annual fee |