ES2435242T3 - Derivados de arilciclopropilacetamida útiles como activadores de glucocinasa - Google Patents
Derivados de arilciclopropilacetamida útiles como activadores de glucocinasa Download PDFInfo
- Publication number
- ES2435242T3 ES2435242T3 ES09768316T ES09768316T ES2435242T3 ES 2435242 T3 ES2435242 T3 ES 2435242T3 ES 09768316 T ES09768316 T ES 09768316T ES 09768316 T ES09768316 T ES 09768316T ES 2435242 T3 ES2435242 T3 ES 2435242T3
- Authority
- ES
- Spain
- Prior art keywords
- solution
- glucose
- compound
- pharmaceutically acceptable
- minutes
- 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.)
- Active
Links
- 102000030595 Glucokinase Human genes 0.000 title description 15
- 108010021582 Glucokinase Proteins 0.000 title description 15
- 239000012190 activator Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 48
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 206010012601 diabetes mellitus Diseases 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000000243 solution Substances 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 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 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000008103 glucose Substances 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 238000001819 mass spectrum Methods 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 229940093499 ethyl acetate Drugs 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 230000008499 blood brain barrier function Effects 0.000 description 5
- 210000001218 blood-brain barrier Anatomy 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 235000011089 carbon dioxide Nutrition 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 230000035699 permeability Effects 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 208000013016 Hypoglycemia Diseases 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 230000002218 hypoglycaemic effect Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- -1 isopropanol 2-pyrrolidin-1-yl-ethanothiol Chemical compound 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- NFRDWNOGNVXNKY-UHFFFAOYSA-N 5-(2-pyrrolidin-1-ylethylsulfanyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC=C1SCCN1CCCC1 NFRDWNOGNVXNKY-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000012594 Earle’s Balanced Salt Solution Substances 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
- 210000005013 brain tissue Anatomy 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- HQQKEXZCAIDKMB-HKUYNNGSSA-N (1r,2s)-2-cyclohexyl-1-(4-cyclopropylsulfonylphenyl)cyclopropane-1-carboxylic acid Chemical compound C1([C@@H]2C[C@]2(C(=O)O)C=2C=CC(=CC=2)S(=O)(=O)C2CC2)CCCCC1 HQQKEXZCAIDKMB-HKUYNNGSSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- LDLDYFCCDKENPD-UHFFFAOYSA-N ethenylcyclohexane Chemical compound C=CC1CCCCC1 LDLDYFCCDKENPD-UHFFFAOYSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 150000007857 hydrazones Chemical class 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 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 2
- 206010022498 insulinoma Diseases 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 208000021255 pancreatic insulinoma Diseases 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- QIIVJLHCZUTGSD-CUBQBAPOSA-N (1r,2s)-2-cyclohexyl-1-(4-cyclopropylsulfonylphenyl)-n-[5-(2-pyrrolidin-1-ylethylsulfanyl)-1,3-thiazol-2-yl]cyclopropane-1-carboxamide Chemical compound O=C([C@]1([C@@H](C1)C1CCCCC1)C=1C=CC(=CC=1)S(=O)(=O)C1CC1)NC(S1)=NC=C1SCCN1CCCC1 QIIVJLHCZUTGSD-CUBQBAPOSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ZVHIZOUBNZLXAE-UHFFFAOYSA-N 2-(4-cyclopropylsulfonylphenyl)-2-diazoacetic acid Chemical compound C1(CC1)S(=O)(=O)C1=CC=C(C=C1)C(C(=O)O)=[N+]=[N-] ZVHIZOUBNZLXAE-UHFFFAOYSA-N 0.000 description 1
- NEEPAIYLSIGNCV-UHFFFAOYSA-N 2-(4-cyclopropylsulfonylphenyl)-2-diazonio-1-ethoxyethenolate Chemical compound C1=CC(C(=[N+]=[N-])C(=O)OCC)=CC=C1S(=O)(=O)C1CC1 NEEPAIYLSIGNCV-UHFFFAOYSA-N 0.000 description 1
- RWZVWUQSFBQAJI-UHFFFAOYSA-N 2-(4-cyclopropylsulfonylphenyl)-2-oxoacetic acid Chemical compound C1=CC(C(=O)C(=O)O)=CC=C1S(=O)(=O)C1CC1 RWZVWUQSFBQAJI-UHFFFAOYSA-N 0.000 description 1
- FJOXVWJOCNVDDI-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanethiol Chemical compound SCCN1CCCC1 FJOXVWJOCNVDDI-UHFFFAOYSA-N 0.000 description 1
- ICGLPKIVTVWCFT-UHFFFAOYSA-N 4-methylbenzenesulfonohydrazide Chemical compound CC1=CC=C(S(=O)(=O)NN)C=C1 ICGLPKIVTVWCFT-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 102000002794 Glucosephosphate Dehydrogenase Human genes 0.000 description 1
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 241000192130 Leuconostoc mesenteroides Species 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000001517 counterregulatory effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- HMIRZQZAFDKCFI-FPOVZHCZSA-N ethyl (1r,2s)-2-cyclohexyl-1-(4-cyclopropylsulfonylphenyl)cyclopropane-1-carboxylate Chemical compound C1([C@@H]2C[C@]2(C(=O)OCC)C=2C=CC(=CC=2)S(=O)(=O)C2CC2)CCCCC1 HMIRZQZAFDKCFI-FPOVZHCZSA-N 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 150000002303 glucose derivatives Chemical class 0.000 description 1
- 230000010030 glucose lowering effect Effects 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 238000002514 liquid chromatography mass spectrum Methods 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000007410 oral glucose tolerance test Methods 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001373 regressive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P3/08—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Emergency Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08380341 | 2008-12-19 | ||
| EP08380341 | 2008-12-19 | ||
| US15378109P | 2009-02-19 | 2009-02-19 | |
| US153781P | 2009-02-19 | ||
| PCT/US2009/067603 WO2010080333A1 (en) | 2008-12-19 | 2009-12-11 | Arylcyclopropylacetamide derivatives useful as glucokinase activators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2435242T3 true ES2435242T3 (es) | 2013-12-17 |
Family
ID=40545955
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09768316T Active ES2435242T3 (es) | 2008-12-19 | 2009-12-11 | Derivados de arilciclopropilacetamida útiles como activadores de glucocinasa |
Country Status (34)
| Country | Link |
|---|---|
| US (1) | US8063079B2 (https=) |
| EP (1) | EP2379517B1 (https=) |
| JP (1) | JP5497064B2 (https=) |
| KR (1) | KR101290437B1 (https=) |
| CN (1) | CN102256952B (https=) |
| AR (1) | AR074470A1 (https=) |
| AU (1) | AU2009335931B2 (https=) |
| BR (1) | BRPI0923183B1 (https=) |
| CA (1) | CA2746746C (https=) |
| CO (1) | CO6382120A2 (https=) |
| CR (1) | CR20110342A (https=) |
| DK (1) | DK2379517T3 (https=) |
| DO (1) | DOP2011000197A (https=) |
| EA (1) | EA019055B1 (https=) |
| EC (1) | ECSP11011150A (https=) |
| ES (1) | ES2435242T3 (https=) |
| HR (1) | HRP20130983T1 (https=) |
| IL (1) | IL213210A (https=) |
| JO (1) | JO2979B1 (https=) |
| MA (1) | MA32902B1 (https=) |
| MX (1) | MX2011006434A (https=) |
| MY (1) | MY180567A (https=) |
| NZ (1) | NZ592930A (https=) |
| PA (1) | PA8851901A1 (https=) |
| PE (1) | PE20120339A1 (https=) |
| PL (1) | PL2379517T3 (https=) |
| PT (1) | PT2379517E (https=) |
| SG (1) | SG172256A1 (https=) |
| SI (1) | SI2379517T1 (https=) |
| TN (1) | TN2011000294A1 (https=) |
| TW (1) | TWI395748B (https=) |
| UA (1) | UA104742C2 (https=) |
| WO (1) | WO2010080333A1 (https=) |
| ZA (1) | ZA201103944B (https=) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102959076B (zh) | 2010-03-31 | 2015-09-16 | 斯克里普斯研究所 | 重编程细胞 |
| CN105899192B (zh) | 2013-11-22 | 2019-08-13 | 国立大学法人东京大学 | 药物递送用载体、偶联物及含有这些成分的组合物以及它们的施予方法 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA02010745A (es) | 2000-05-03 | 2003-03-10 | Hoffmann La Roche | Activadores de glucocinasa heteroaromaticos de alquinil-fenilo. |
| DK1282611T3 (da) | 2000-05-08 | 2005-02-14 | Hoffmann La Roche | Substituerede phenylacetatamider og anvendelse deraf som glucokinaseaktivatorer |
| WO2001085707A1 (en) | 2000-05-08 | 2001-11-15 | F. Hoffmann-La Roche Ag | Para-amine substituted phenylamide glucokinase activators |
| MY141521A (en) * | 2002-12-12 | 2010-05-14 | Hoffmann La Roche | 5-substituted-six-membered heteroaromatic glucokinase activators |
| DE60336850D1 (en) | 2003-01-06 | 2011-06-01 | Lilly Co Eli | Substituierte arylcyclopropylacetamide als glucokinaseaktivatoren |
| PL378117A1 (pl) | 2003-02-11 | 2006-03-06 | Prosidion Limited | Tricyklopodstawione związki amidowe |
| US7262196B2 (en) | 2003-02-11 | 2007-08-28 | Prosidion Limited | Tri(cyclo) substituted amide glucokinase activator compounds |
| US7432287B2 (en) * | 2003-02-26 | 2008-10-07 | Banyu Pharmeceutical Co., Ltd. | Heteroarylcarbamoylbenzene derivative |
| MXPA06012008A (es) | 2004-04-21 | 2007-01-25 | Prosidion Ltd | Compuestos de amida tri(ciclo) sustituidos. |
| KR100890695B1 (ko) | 2004-08-12 | 2009-03-26 | 프로시디온 리미티드 | 치환된 페닐아세트아미드 및 글루코키나제 활성화제로서의그의 용도 |
| EP1824835A1 (en) * | 2004-12-03 | 2007-08-29 | Novo Nordisk A/S | Heteroaromatic glucokinase activators |
| RU2008103142A (ru) * | 2005-07-01 | 2009-08-10 | Новартис АГ (CH) | Комбинация органических соединений |
| JP4033409B1 (ja) | 2005-07-11 | 2008-01-16 | 田辺三菱製薬株式会社 | オキシム誘導体及びその製法 |
| JP2009504621A (ja) * | 2005-08-09 | 2009-02-05 | アストラゼネカ アクチボラグ | 糖尿病の処置のためのヘテロアリールカルバモイルベンゼン誘導体 |
| WO2007051845A1 (en) | 2005-11-03 | 2007-05-10 | Prosidion Ltd | Tricyclo substituted amides |
| US20080293741A1 (en) * | 2005-11-03 | 2008-11-27 | Matthew Colin Thor Fyfe | Tricyclo Substituted Amides as Glucokinase Modulators |
| WO2007051846A1 (en) | 2005-11-03 | 2007-05-10 | Prosidion Ltd | Tricyclo substituted amides |
| KR20090025358A (ko) * | 2006-07-24 | 2009-03-10 | 에프. 호프만-라 로슈 아게 | 글루코키나제 활성화제로서의 피라졸 |
| EP2105435A4 (en) * | 2007-01-10 | 2011-06-15 | Mitsubishi Tanabe Pharma Corp | Hydrazone derivative |
| KR101608259B1 (ko) | 2008-04-28 | 2016-04-01 | 교린 세이야꾸 가부시키 가이샤 | 시클로펜틸아크릴산아미드 유도체 |
-
2009
- 2009-11-12 UA UAA201107562A patent/UA104742C2/uk unknown
- 2009-12-03 PA PA20098851901A patent/PA8851901A1/es unknown
- 2009-12-03 AR ARP090104672A patent/AR074470A1/es active IP Right Grant
- 2009-12-04 TW TW098141556A patent/TWI395748B/zh active
- 2009-12-06 JO JO2009467A patent/JO2979B1/en active
- 2009-12-11 MX MX2011006434A patent/MX2011006434A/es active IP Right Grant
- 2009-12-11 EA EA201170845A patent/EA019055B1/ru not_active IP Right Cessation
- 2009-12-11 KR KR1020117014073A patent/KR101290437B1/ko not_active Expired - Fee Related
- 2009-12-11 ES ES09768316T patent/ES2435242T3/es active Active
- 2009-12-11 PE PE2011001220A patent/PE20120339A1/es active IP Right Grant
- 2009-12-11 PL PL09768316T patent/PL2379517T3/pl unknown
- 2009-12-11 WO PCT/US2009/067603 patent/WO2010080333A1/en not_active Ceased
- 2009-12-11 BR BRPI0923183-8A patent/BRPI0923183B1/pt not_active IP Right Cessation
- 2009-12-11 NZ NZ592930A patent/NZ592930A/xx not_active IP Right Cessation
- 2009-12-11 CN CN200980150686XA patent/CN102256952B/zh active Active
- 2009-12-11 AU AU2009335931A patent/AU2009335931B2/en not_active Ceased
- 2009-12-11 SI SI200930713T patent/SI2379517T1/sl unknown
- 2009-12-11 PT PT97683163T patent/PT2379517E/pt unknown
- 2009-12-11 US US12/635,758 patent/US8063079B2/en active Active
- 2009-12-11 SG SG2011044823A patent/SG172256A1/en unknown
- 2009-12-11 HR HRP20130983AT patent/HRP20130983T1/hr unknown
- 2009-12-11 EP EP09768316.3A patent/EP2379517B1/en active Active
- 2009-12-11 MY MYPI2011002765A patent/MY180567A/en unknown
- 2009-12-11 DK DK09768316.3T patent/DK2379517T3/da active
- 2009-12-11 JP JP2011542276A patent/JP5497064B2/ja active Active
- 2009-12-11 CA CA2746746A patent/CA2746746C/en active Active
-
2011
- 2011-05-27 ZA ZA2011/03944A patent/ZA201103944B/en unknown
- 2011-05-30 IL IL213210A patent/IL213210A/en active IP Right Grant
- 2011-06-09 TN TN2011000294A patent/TN2011000294A1/fr unknown
- 2011-06-14 MA MA33945A patent/MA32902B1/fr unknown
- 2011-06-17 CR CR20110342A patent/CR20110342A/es unknown
- 2011-06-17 EC EC2011011150A patent/ECSP11011150A/es unknown
- 2011-06-17 DO DO2011000197A patent/DOP2011000197A/es unknown
- 2011-06-23 CO CO11079303A patent/CO6382120A2/es active IP Right Grant
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2663789T3 (es) | Compuesto de pirazol-amida y usos medicinales del mismo | |
| US9408845B2 (en) | Formulations containing pyridazine compounds | |
| ES2448498T3 (es) | Atropisómero de derivado de pirrol | |
| WO2013158649A1 (en) | Compositions and methods of modulating 15-pgdh activity | |
| BR112021001881A2 (pt) | compostos de 2,6-diaminopiridina | |
| ES2731802T3 (es) | Derivados de naftiridinodiona como supresores de mutaciones sin sentido | |
| WO2016127916A1 (zh) | 作为长效dpp-iv抑制剂的取代的氨基六元饱和杂脂环类 | |
| Kalinin et al. | Highly hydrophilic 1, 3-oxazol-5-yl benzenesulfonamide inhibitors of carbonic anhydrase II for reduction of glaucoma-related intraocular pressure | |
| ES2435242T3 (es) | Derivados de arilciclopropilacetamida útiles como activadores de glucocinasa | |
| TWI764977B (zh) | 作爲ｃａｓｐａｓｅ抑制劑的聯環化合物、含有其的藥物組合物及其應用 | |
| JP2012505921A (ja) | 低酸素性損傷または虚血性損傷を治療しまたは予防するための組成物および方法 | |
| ES2934533T3 (es) | Cristal y sal del compuesto 4-(naftalen-1-il)-4H-1,2,4-triazol y método para su preparación | |
| EP3524240A1 (en) | Urea derivative | |
| CA2887420C (en) | Matrix metalloproteinase inhibitors and methods for the treatment of pain and other diseases | |
| Zhang et al. | Discovery of 1-Difluoromethyl-3-(3-cyanophenyl)-6-[4-(trifluoromethoxy) phenyl] imidazo [1, 5-a] pyrazin-8-(7 H)-one as a Potent P2Y1 Antagonist for the Treatment of Ischemic Stroke and Myocardial Infarction | |
| HK1159635B (en) | Arylcyclopropylacetamide derivatives useful as glucokinase activators | |
| HK1159635A (en) | Arylcyclopropylacetamide derivatives useful as glucokinase activators | |
| WO2022159566A1 (en) | Benzenesulfonamide agonists of trap1 for treating organ fibrosis | |
| EP2527322A1 (en) | Carbamyl alkylphenyl disulfide derivatives and their therapeutic uses | |
| SA515361182B1 (ar) | مركب بيرازول-أميد والاستخدامات الدوائية الخاصة به | |
| HK40004848A (en) | Urea derivative |