CA2802541A1 - Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine - Google Patents
Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine Download PDFInfo
- Publication number
- CA2802541A1 CA2802541A1 CA2802541A CA2802541A CA2802541A1 CA 2802541 A1 CA2802541 A1 CA 2802541A1 CA 2802541 A CA2802541 A CA 2802541A CA 2802541 A CA2802541 A CA 2802541A CA 2802541 A1 CA2802541 A1 CA 2802541A1
- Authority
- CA
- Canada
- Prior art keywords
- ethyl
- compound
- pyrimidine
- tetrazol
- thiazol
- 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.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 78
- NFTMKHWBOINJGM-UHFFFAOYSA-N 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-4-[[4-(tetrazol-1-yl)phenoxy]methyl]-1,3-thiazole Chemical group N1=CC(CC)=CN=C1N1CCC(C=2SC=C(COC=3C=CC(=CC=3)N3N=NN=C3)N=2)CC1 NFTMKHWBOINJGM-UHFFFAOYSA-N 0.000 title claims description 73
- 238000000034 method Methods 0.000 claims abstract description 105
- -1 4- tetrazol - 1 -yl -phenoxymethyl Chemical group 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims description 97
- 239000007962 solid dispersion Substances 0.000 claims description 56
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 52
- 238000010922 spray-dried dispersion Methods 0.000 claims description 51
- 229920000642 polymer Polymers 0.000 claims description 45
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims description 42
- 239000008194 pharmaceutical composition Substances 0.000 claims description 37
- 239000002904 solvent Substances 0.000 claims description 36
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 34
- 239000008103 glucose Substances 0.000 claims description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 22
- 241000124008 Mammalia Species 0.000 claims description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 19
- 210000004369 blood Anatomy 0.000 claims description 18
- 239000008280 blood Substances 0.000 claims description 18
- 238000001694 spray drying Methods 0.000 claims description 17
- 238000001035 drying Methods 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical group C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 9
- 235000010944 ethyl methyl cellulose Nutrition 0.000 claims description 9
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 9
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 9
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 9
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 9
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims description 9
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims description 9
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 claims description 9
- 229920003087 methylethyl cellulose Polymers 0.000 claims description 9
- 239000012943 hotmelt Substances 0.000 claims description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 8
- 229920002301 cellulose acetate Polymers 0.000 claims description 7
- 125000005591 trimellitate group Chemical group 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- ZUAAPNNKRHMPKG-UHFFFAOYSA-N acetic acid;butanedioic acid;methanol;propane-1,2-diol Chemical compound OC.CC(O)=O.CC(O)CO.OC(=O)CCC(O)=O ZUAAPNNKRHMPKG-UHFFFAOYSA-N 0.000 claims description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 229920001531 copovidone Polymers 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 229940069328 povidone Drugs 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 claims description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 2
- 238000002844 melting Methods 0.000 claims description 2
- 230000008018 melting Effects 0.000 claims description 2
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 2
- 229940090181 propyl acetate Drugs 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 2
- 230000008023 solidification Effects 0.000 claims 2
- 238000007711 solidification Methods 0.000 claims 2
- JKQCZAKAXNWFFN-UHFFFAOYSA-N butan-2-one;4-methylpentan-2-one Chemical compound CCC(C)=O.CC(C)CC(C)=O JKQCZAKAXNWFFN-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 8
- 229940126062 Compound A Drugs 0.000 description 95
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 95
- 239000000243 solution Substances 0.000 description 56
- 238000009472 formulation Methods 0.000 description 32
- 239000007787 solid Substances 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000000047 product Substances 0.000 description 21
- 230000008569 process Effects 0.000 description 19
- 239000007921 spray Substances 0.000 description 19
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 18
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 18
- 238000012216 screening Methods 0.000 description 18
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 15
- 238000004519 manufacturing process Methods 0.000 description 15
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
- 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 14
- 235000012054 meals Nutrition 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
- 238000004090 dissolution Methods 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 229910052740 iodine Inorganic materials 0.000 description 11
- 229940068196 placebo Drugs 0.000 description 11
- 239000000902 placebo Substances 0.000 description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 239000006185 dispersion Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 239000012530 fluid Substances 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 10
- 229910000024 caesium carbonate Inorganic materials 0.000 description 9
- 235000019359 magnesium stearate Nutrition 0.000 description 9
- 235000011121 sodium hydroxide Nutrition 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 8
- 239000007789 gas Substances 0.000 description 8
- 230000000968 intestinal effect Effects 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 102000004877 Insulin Human genes 0.000 description 7
- 108090001061 Insulin Proteins 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 238000000576 coating method Methods 0.000 description 7
- 229940125396 insulin Drugs 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 238000007410 oral glucose tolerance test Methods 0.000 description 7
- 238000001556 precipitation Methods 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 6
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 239000007888 film coating Substances 0.000 description 6
- 238000009501 film coating Methods 0.000 description 6
- 238000005469 granulation Methods 0.000 description 6
- 230000003179 granulation Effects 0.000 description 6
- 239000000155 melt Substances 0.000 description 6
- 229940016286 microcrystalline cellulose Drugs 0.000 description 6
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 6
- 239000008108 microcrystalline cellulose Substances 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 238000012552 review Methods 0.000 description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 5
- 239000008119 colloidal silica Substances 0.000 description 5
- 229960000913 crospovidone Drugs 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000003914 insulin secretion Effects 0.000 description 5
- 239000011630 iodine Substances 0.000 description 5
- 229960001021 lactose monohydrate Drugs 0.000 description 5
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 5
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- 235000017550 sodium carbonate Nutrition 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- BGLLZQRUXJGTAD-UHFFFAOYSA-N 2-chloro-5-ethylpyrimidine Chemical compound CCC1=CN=C(Cl)N=C1 BGLLZQRUXJGTAD-UHFFFAOYSA-N 0.000 description 4
- AXJKWXIVFCNRCQ-UHFFFAOYSA-N 4-(tetrazol-1-yl)phenol Chemical compound C1=CC(O)=CC=C1N1N=NN=C1 AXJKWXIVFCNRCQ-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 102100021198 Chemerin-like receptor 2 Human genes 0.000 description 4
- 229920003134 Eudragit® polymer Polymers 0.000 description 4
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 4
- 101000750094 Homo sapiens Chemerin-like receptor 2 Proteins 0.000 description 4
- 229920003083 Kollidon® VA64 Polymers 0.000 description 4
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 4
- 102100040918 Pro-glucagon Human genes 0.000 description 4
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 4
- 238000007908 dry granulation Methods 0.000 description 4
- 238000001125 extrusion Methods 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 230000003285 pharmacodynamic effect Effects 0.000 description 4
- 201000009104 prediabetes syndrome Diseases 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 230000004936 stimulating effect Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 210000002700 urine Anatomy 0.000 description 4
- 235000013311 vegetables Nutrition 0.000 description 4
- 229920003119 EUDRAGIT E PO Polymers 0.000 description 3
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 3
- 102000051325 Glucagon Human genes 0.000 description 3
- 108060003199 Glucagon Proteins 0.000 description 3
- 208000002705 Glucose Intolerance Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 208000001280 Prediabetic State Diseases 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 238000007605 air drying Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 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 3
- NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 239000012738 dissolution medium Substances 0.000 description 3
- 238000007922 dissolution test Methods 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 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 3
- 229960004666 glucagon Drugs 0.000 description 3
- 230000010030 glucose lowering effect Effects 0.000 description 3
- 229920001903 high density polyethylene Polymers 0.000 description 3
- 239000004700 high-density polyethylene Substances 0.000 description 3
- MGXWVYUBJRZYPE-YUGYIWNOSA-N incretin Chemical class C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=C(O)C=C1 MGXWVYUBJRZYPE-YUGYIWNOSA-N 0.000 description 3
- 239000000859 incretin Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000001095 magnesium carbonate Substances 0.000 description 3
- 235000014380 magnesium carbonate Nutrition 0.000 description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 3
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 239000003495 polar organic solvent Substances 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 238000009597 pregnancy test Methods 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- SUNMBRGCANLOEG-UHFFFAOYSA-N 1,3-dichloroacetone Chemical compound ClCC(=O)CCl SUNMBRGCANLOEG-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 101150041968 CDC13 gene Proteins 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 238000012369 In process control Methods 0.000 description 2
- 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 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 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
- 239000007832 Na2SO4 Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 229940124301 concurrent medication Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000002274 desiccant Substances 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 210000003890 endocrine cell Anatomy 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 239000012527 feed solution Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 230000009477 glass transition Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000003988 headspace gas chromatography Methods 0.000 description 2
- 238000010965 in-process control Methods 0.000 description 2
- 210000004153 islets of langerhan Anatomy 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 229920001684 low density polyethylene Polymers 0.000 description 2
- 239000004702 low-density polyethylene Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 231100000682 maximum tolerated dose Toxicity 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 238000003801 milling Methods 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 238000000634 powder X-ray diffraction Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000010129 solution processing Methods 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- YHFUWPUJUMZXBD-UHFFFAOYSA-N tert-butyl 4-carbamoylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C(N)=O)CC1 YHFUWPUJUMZXBD-UHFFFAOYSA-N 0.000 description 2
- 229920003169 water-soluble polymer Polymers 0.000 description 2
- KOFLVDBWRHFSAB-UHFFFAOYSA-N 1,2,4,5-tetrahydro-1-(phenylmethyl)-5,9b(1',2')-benzeno-9bh-benz(g)indol-3(3ah)-one Chemical compound C1C(C=2C3=CC=CC=2)C2=CC=CC=C2C23C1C(=O)CN2CC1=CC=CC=C1 KOFLVDBWRHFSAB-UHFFFAOYSA-N 0.000 description 1
- WUFBCYQFXNABJT-UHFFFAOYSA-N 4-(chloromethyl)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-1,3-thiazole Chemical compound N1=CC(CC)=CN=C1N1CCC(C=2SC=C(CCl)N=2)CC1 WUFBCYQFXNABJT-UHFFFAOYSA-N 0.000 description 1
- WVVJEIQJCDUVSP-UHFFFAOYSA-N 4-carbamothioylpiperidine-1-carboxylic acid Chemical compound NC(=S)C1CCN(C(O)=O)CC1 WVVJEIQJCDUVSP-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241001631457 Cannula Species 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 108010004460 Gastric Inhibitory Polypeptide Proteins 0.000 description 1
- 102100039994 Gastric inhibitory polypeptide Human genes 0.000 description 1
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010056997 Impaired fasting glucose Diseases 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 238000007681 bariatric surgery Methods 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- MYTMXVHNEWBFAL-UHFFFAOYSA-L dipotassium;carbonate;hydrate Chemical class O.[K+].[K+].[O-]C([O-])=O MYTMXVHNEWBFAL-UHFFFAOYSA-L 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000006362 insulin response pathway Effects 0.000 description 1
- 230000037041 intracellular level Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000001948 isotopic labelling Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000005367 kimax Substances 0.000 description 1
- 229910052743 krypton Inorganic materials 0.000 description 1
- DNNSSWSSYDEUBZ-UHFFFAOYSA-N krypton atom Chemical compound [Kr] DNNSSWSSYDEUBZ-UHFFFAOYSA-N 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- 230000005226 mechanical processes and functions Effects 0.000 description 1
- 238000011177 media preparation Methods 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012806 monitoring device Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 230000012666 negative regulation of transcription by glucose Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 1
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical class [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
- 238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- OISDRMFIITXOTB-UHFFFAOYSA-N tert-butyl 4-[4-(chloromethyl)-1,3-thiazol-2-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=NC(CCl)=CS1 OISDRMFIITXOTB-UHFFFAOYSA-N 0.000 description 1
- SCGQNJHAAYUQOO-UHFFFAOYSA-N tert-butyl 4-carbamothioylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C(N)=S)CC1 SCGQNJHAAYUQOO-UHFFFAOYSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61P3/08—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D417/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35798110P | 2010-06-23 | 2010-06-23 | |
| US61/357,981 | 2010-06-23 | ||
| PCT/US2011/040972 WO2011163090A1 (en) | 2010-06-23 | 2011-06-17 | Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2802541A1 true CA2802541A1 (en) | 2011-12-29 |
Family
ID=44584703
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2802541A Abandoned CA2802541A1 (en) | 2010-06-23 | 2011-06-17 | Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US9241924B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2585048B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP5847813B2 (cg-RX-API-DMAC7.html) |
| CN (2) | CN109674753A (cg-RX-API-DMAC7.html) |
| BR (1) | BR112012032248A2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2802541A1 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2676209T3 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2011163090A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7638541B2 (en) | 2006-12-28 | 2009-12-29 | Metabolex Inc. | 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| CA2693169C (en) | 2007-07-19 | 2016-01-12 | Metabolex, Inc. | N-linked heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
| WO2009123992A1 (en) * | 2008-03-31 | 2009-10-08 | Metabolex, Inc. | Oxymethylene aryl compounds and uses thereof |
| US20110160222A1 (en) * | 2008-11-26 | 2011-06-30 | Metabolex, Inc. | Modulators of glucose homeostasis for the treatment of diabetes and metabolic disorders |
| JP5909185B2 (ja) * | 2009-10-01 | 2016-04-26 | シマベイ セラピューティクス， インコーポレーテッド | 置換テトラゾール−１−イルフェノキシメチルチアゾール−２−イルピペリジニルピリミジン塩 |
| WO2011163090A1 (en) | 2010-06-23 | 2011-12-29 | Metabolex, Inc. | Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| KR20160104709A (ko) * | 2013-12-31 | 2016-09-05 | 아센디아 파마슈티컬스, 엘엘씨 | 난수용성 화합물용 약제학적 조성물 |
| ES2753582T3 (es) * | 2014-06-11 | 2020-04-13 | Bayer Cropscience Ag | Preparación de piperidin-4-carbotioamida |
| US10292983B2 (en) | 2016-08-03 | 2019-05-21 | Cymabay Therapeutics, Inc. | Oxymethylene aryl compounds for treating inflammatory gastrointestinal diseases or gastrointestinal conditions |
| CA3173731A1 (en) | 2020-02-28 | 2021-09-02 | Kallyope, Inc. | Gpr40 agonists |
| CA3178994A1 (en) | 2020-05-19 | 2021-11-25 | Iyassu Sebhat | Ampk activators |
| WO2021263039A1 (en) | 2020-06-26 | 2021-12-30 | Kallyope, Inc. | Ampk activators |
Family Cites Families (99)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3108117A (en) | 1959-02-12 | 1963-10-22 | Mead Johnson & Co | 3-benzyl-1, 2-diloweralkyl-3-pyrrolidinols |
| US3778443A (en) | 1969-02-13 | 1973-12-11 | Ciba Geigy Ag | 4-tetrahydro pyridyl,hydroxy alkyl pyrazoles |
| US3536809A (en) | 1969-02-17 | 1970-10-27 | Alza Corp | Medication method |
| US3598123A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
| US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
| GB1422263A (en) | 1973-01-30 | 1976-01-21 | Ferrosan As | 4-phenyl-piperidine compounds |
| US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
| DE2701705A1 (de) | 1976-01-28 | 1977-08-04 | Sandoz Ag | Neue organische verbindungen, ihre verwendung und herstellung |
| US4008719A (en) | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
| CA1146866A (en) | 1979-07-05 | 1983-05-24 | Yamanouchi Pharmaceutical Co. Ltd. | Process for the production of sustained release pharmaceutical composition of solid medical material |
| DE3438830A1 (de) | 1984-10-23 | 1986-04-30 | Rentschler Arzneimittel | Nifedipin enthaltende darreichungsform und verfahren zu ihrer herstellung |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| WO1992018106A1 (fr) * | 1991-04-16 | 1992-10-29 | Nippon Shinyaku Co., Ltd. | Procede de production d'une dispersion solide |
| US5817667A (en) | 1991-04-17 | 1998-10-06 | University Of Georgia Research Foudation | Compounds and methods for the treatment of cancer |
| US5340591A (en) | 1992-01-24 | 1994-08-23 | Fujisawa Pharmaceutical Co., Ltd. | Method of producing a solid dispersion of the sparingly water-soluble drug, nilvadipine |
| JP3265680B2 (ja) | 1992-03-12 | 2002-03-11 | 大正製薬株式会社 | 経口製剤用組成物 |
| AU4444393A (en) | 1992-09-01 | 1994-03-10 | Zeneca Limited | Pyrrolidine derivatives |
| GB9310713D0 (en) | 1993-05-24 | 1993-07-07 | Zeneca Ltd | Aryl substituted heterocycles |
| ATE279406T1 (de) | 1995-01-12 | 2004-10-15 | Glaxo Group Ltd | Piperidinderivate mit tachykinin-antagonistischer wirkung |
| KR100533431B1 (ko) | 1995-01-23 | 2006-05-03 | 다이이치 아스비오파마 가부시키가이샤 | 허혈성질환에기인하는증상의완화또는치료용약제및이에유용한화합물 |
| DE19504832A1 (de) | 1995-02-14 | 1996-08-22 | Basf Ag | Feste Wirkstoff-Zubereitungen |
| PT863875E (pt) | 1995-09-07 | 2003-10-31 | Hoffmann La Roche | Novos compostos 4-(oxialcoxifenil)-3-oxi-piperidina para o tratamento de insuficiencia cardiaca e renal |
| JPH11513382A (ja) | 1995-10-20 | 1999-11-16 | ドクトル カルル トーマエ ゲゼルシャフト ミット ベシュレンクテル ハフツング | ５員複素環化合物、これらの化合物を含む医薬品、それらの使用及びそれらの調製方法 |
| AU710594B2 (en) | 1996-07-22 | 1999-09-23 | Asubio Pharma Co., Ltd. | Arylpiperidinol and arylpiperidine derivatives and pharmaceuticals containing the same |
| DK0901786T3 (da) | 1997-08-11 | 2007-10-08 | Pfizer Prod Inc | Faste farmaceutiske dispersioner med foröget biotilgængelighed |
| US6274735B1 (en) | 1998-08-10 | 2001-08-14 | Hoffmann-La Roche Inc. | Process and intermediates for preparation of substituted piperidines |
| IT1303737B1 (it) | 1998-11-11 | 2001-02-23 | Smithkline Beecham Spa | Derivati fenilpiperidinici procedimento per la loro preparazione eloro uso come ligandi del recettore orl-1. |
| US20030017528A1 (en) | 1998-11-20 | 2003-01-23 | Ruoping Chen | Human orphan G protein-coupled receptors |
| KR100926208B1 (ko) | 1998-11-20 | 2009-11-09 | 아레나 파마슈티칼스, 인크. | 사람의 오르판 ｇ 단백질 커플링 수용체 |
| DE60039379D1 (de) * | 1999-02-10 | 2008-08-21 | Pfizer Prod Inc | Pharmazeutische feste Dispersionen |
| US6221660B1 (en) | 1999-02-22 | 2001-04-24 | Synaptic Pharmaceutical Corporation | DNA encoding SNORF25 receptor |
| GB9912416D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| GB9923177D0 (en) | 1999-09-30 | 1999-12-01 | Pfizer Ltd | Novel polypeptide |
| IL139073A0 (en) | 1999-10-21 | 2001-11-25 | Pfizer | Treatment of neuropathy |
| EP1176147A1 (en) | 2000-07-28 | 2002-01-30 | Pfizer Limited | Process for the preparation of pyrazolo[4,3-d]pyrimidin-7-ones and intermediates thereof |
| US6784185B2 (en) | 2001-03-16 | 2004-08-31 | Pfizer Inc. | Pharmaceutically active compounds |
| US6770645B2 (en) | 2001-03-16 | 2004-08-03 | Pfizer Inc. | Pharmaceutically active compounds |
| US20030095958A1 (en) | 2001-04-27 | 2003-05-22 | Bhisetti Govinda R. | Inhibitors of bace |
| US20030003157A1 (en) | 2001-06-06 | 2003-01-02 | University Of Medicine & Dentistry Of New Jersey | Collagen compositions and methods for making and using the same |
| CA2456754A1 (en) | 2001-08-08 | 2003-02-20 | Yuji Iizawa | Benzazepine derivative, process for producing the same, and use |
| WO2003063821A2 (en) * | 2002-02-01 | 2003-08-07 | Pfizer Products Inc. | Method for making homogeneous spray-dried solid amorphous drug dispersions using pressure nozzles |
| WO2003091216A1 (en) | 2002-04-25 | 2003-11-06 | Sumitomo Pharmaceuticals Co., Ltd. | Novel piperidine derivative |
| GB0224919D0 (en) | 2002-10-25 | 2002-12-04 | Pfizer Ltd | Triazole compounds useful in therapy |
| GB0230162D0 (en) | 2002-12-24 | 2003-02-05 | Metris Therapeutics Ltd | Compounds useful in inhibiting angiogenesis |
| MXPA05009247A (es) | 2003-03-05 | 2006-05-19 | Macchine Utensili Speciali S P | Metodo de maquinado de un disco de freno. |
| GB0308333D0 (en) | 2003-04-10 | 2003-05-14 | Glaxo Group Ltd | Novel compounds |
| EP1633737A1 (en) | 2003-06-13 | 2006-03-15 | Schering Aktiengesellschaft | Quinolyl amide derivatives as ccr-5 antagonists |
| EP2287165A3 (en) | 2003-07-14 | 2011-06-22 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
| CA2533898A1 (en) | 2003-07-29 | 2005-02-10 | Xenon Pharmaceuticals Inc. | Pyridyl derivatives and their use as therapeutic agents |
| FR2862647B1 (fr) | 2003-11-25 | 2008-07-04 | Aventis Pharma Sa | Derives de pyrazolyle, procede de preparation et intermediaires de ce procede a titre de medicaments et de compositions pharmaceutiques les renfermant |
| US7235641B2 (en) | 2003-12-22 | 2007-06-26 | Micromet Ag | Bispecific antibodies |
| EP1711491A1 (en) | 2003-12-24 | 2006-10-18 | Prosidion Limited | Heterocyclic derivatives as gpcr receptor agonists |
| TW200538433A (en) | 2004-02-24 | 2005-12-01 | Irm Llc | Immunosuppressant compounds and compositiions |
| BRPI0511907A8 (pt) | 2004-06-08 | 2018-05-02 | A Carlsson Res Ab | novos derivados de fenilpiperidinas/piperazinas dissubstituídos como moduladores da neurotransmissão de dopamina |
| PT1852433E (pt) | 2004-10-29 | 2012-02-08 | Zeria Pharm Co Ltd | Derivados de carbazole, seus solvatos ou seus sais farmaceuticamente aceitáveis |
| TW200633990A (en) | 2004-11-18 | 2006-10-01 | Takeda Pharmaceuticals Co | Amide compound |
| GB0428526D0 (en) | 2004-12-30 | 2005-02-09 | Novartis Ag | Organic compounds |
| EP1841760B1 (en) | 2004-12-30 | 2011-08-10 | Exelixis, Inc. | Pyrimidine derivatives as kinase modulators and method of use |
| DOP2006000008A (es) | 2005-01-10 | 2006-08-31 | Arena Pharm Inc | Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1 |
| MY148521A (en) | 2005-01-10 | 2013-04-30 | Arena Pharm Inc | Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto |
| US8277495B2 (en) | 2005-01-13 | 2012-10-02 | Candela Corporation | Method and apparatus for treating a diseased nail |
| US7879838B2 (en) | 2005-02-16 | 2011-02-01 | Schering Corporation | Heteroaryl substituted pyrazinyl-piperazine-piperidines with CXCR3 antagonist activity |
| EP1888529A2 (en) | 2005-05-18 | 2008-02-20 | Wyeth | 3-cyanoquinoline inhibitors of tpl2 kinase and methods of making and using the same |
| US20090170907A1 (en) | 2005-06-06 | 2009-07-02 | Smithkline Beecham Corporation | Chemical Compounds |
| WO2006134487A1 (en) | 2005-06-15 | 2006-12-21 | Pfizer Limited | 3-phenylazetidine derivatives as dopamine agonists |
| US20090018123A1 (en) | 2005-06-20 | 2009-01-15 | Milind D Sindkhedkar | Oxazolidinones Bearing Antimicrobial Activity Composition and Methods of Preparation |
| US20090325924A1 (en) | 2005-06-30 | 2009-12-31 | Stuart Edward | GPCR Agonists |
| JP2008545008A (ja) | 2005-06-30 | 2008-12-11 | プロシディオン・リミテッド | Ｇｐｃｒアゴニスト |
| BRPI0616245A2 (pt) | 2005-09-16 | 2011-06-14 | Arena Pharm Inc | modulador de metabolismo, seus usos, composiÇço farmaceutica compreendendo o mesmo, bem como mÉtodo para produÇço da referida composiÇço |
| CN101272784A (zh) | 2005-09-29 | 2008-09-24 | 塞诺菲-安万特股份有限公司 | 苯基-和吡啶基-1,2,4-噁二唑酮衍生物、它们的制备方法和它们作为药物的用途 |
| WO2007066189A2 (en) * | 2005-12-09 | 2007-06-14 | Pfizer Products Inc. | Salts, prodrugs and formulations of 1-[5-(4-amino-7-isopropyl-7h-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-2-methoxy-phenyl]-3-(2,4-dichloro-phenyl)-urea |
| PE20071221A1 (es) | 2006-04-11 | 2007-12-14 | Arena Pharm Inc | Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas |
| EP2043744A2 (en) | 2006-07-13 | 2009-04-08 | SmithKline Beecham Corporation | Chemical compounds |
| US8343548B2 (en) * | 2006-08-08 | 2013-01-01 | Shin-Etsu Chemical Co., Ltd. | Solid dosage form comprising solid dispersion |
| WO2008025798A1 (en) | 2006-08-30 | 2008-03-06 | Biovitrum Ab (Publ) | Pyridine compounds for treating gpr119 related disorders |
| DE602007008470D1 (en) * | 2006-10-17 | 2010-09-23 | Bend Res Inc | Off |
| CN101657471B (zh) | 2006-12-06 | 2013-07-03 | 史密丝克莱恩比彻姆公司 | 二环化合物及其作为抗糖尿病药的用途 |
| US7638541B2 (en) * | 2006-12-28 | 2009-12-29 | Metabolex Inc. | 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| TWI414523B (zh) * | 2006-12-28 | 2013-11-11 | Metabolex Inc | 用於治療糖尿病及代謝病症之雜環受體促效劑 |
| AU2008222812B2 (en) | 2007-03-08 | 2012-03-22 | Irm Llc | Compounds and compositions as modulators of GPR119 activity |
| EP2014656A3 (en) | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| CA2693169C (en) | 2007-07-19 | 2016-01-12 | Metabolex, Inc. | N-linked heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
| FR2918986B1 (fr) | 2007-07-19 | 2009-09-04 | Sanofi Aventis Sa | Derives de 6-cycloamino-3-(pyridazin-4-yl)imidazo[1,2-b]- pyridazine, leur preparation et leur application en therapeutique |
| US8293747B2 (en) | 2007-07-19 | 2012-10-23 | Merck Sharp & Dohme Corp. | Heterocyclic amide compounds as protein kinase inhibitors |
| AU2008277796A1 (en) | 2007-07-19 | 2009-01-22 | F. Hoffmann-La Roche Ag | Novel heterocyclyl compounds and their use as chemokine antagonists |
| UY31232A1 (es) | 2007-07-19 | 2009-03-02 | Compuestos derivados de dibenzotifenilamino-cromen-4-onas activas sustituidas y sus isomeros y aplicaciones | |
| ES2435779T3 (es) | 2007-07-19 | 2013-12-23 | Sanofi | Agentes citotóxicos que comprenden nuevos derivados de tomaimicina y su uso terapéutico |
| AU2008331456A1 (en) | 2007-12-04 | 2009-06-11 | Merck Frosst Canada Ltd | Renin inhibitors |
| WO2009123992A1 (en) * | 2008-03-31 | 2009-10-08 | Metabolex, Inc. | Oxymethylene aryl compounds and uses thereof |
| BRPI0914891A2 (pt) | 2008-06-20 | 2015-11-24 | Metabolex Inc | agonistas de aril gpr119 e usos dos mesmos |
| WO2010013849A1 (ja) | 2008-08-01 | 2010-02-04 | 日本ケミファ株式会社 | Ｇｐｒ１１９作動薬 |
| MX2011002558A (es) * | 2008-09-10 | 2011-04-26 | Boehringer Ingelheim Int | Terapia de combinacion para el tratamiento de diabetes y estados relacionados. |
| WO2010048149A2 (en) | 2008-10-20 | 2010-04-29 | Kalypsys, Inc. | Heterocyclic modulators of gpr119 for treatment of disease |
| US20110160222A1 (en) | 2008-11-26 | 2011-06-30 | Metabolex, Inc. | Modulators of glucose homeostasis for the treatment of diabetes and metabolic disorders |
| JP5667180B2 (ja) | 2009-07-01 | 2015-02-12 | イオン メディックス インコーポレイテッド | 哺乳類の有核細胞に由来するマイクロベシクル及びその用途 |
| JP5909185B2 (ja) * | 2009-10-01 | 2016-04-26 | シマベイ セラピューティクス， インコーポレーテッド | 置換テトラゾール−１−イルフェノキシメチルチアゾール−２−イルピペリジニルピリミジン塩 |
| WO2011153435A1 (en) | 2010-06-04 | 2011-12-08 | Metabolex, Inc. | Preparation of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| WO2011163090A1 (en) | 2010-06-23 | 2011-12-29 | Metabolex, Inc. | Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| US20120184572A1 (en) | 2011-01-13 | 2012-07-19 | Metabolex, Inc. | Aryl gpr119 agonists and uses thereof |
-
2011
- 2011-06-17 WO PCT/US2011/040972 patent/WO2011163090A1/en not_active Ceased
- 2011-06-17 BR BR112012032248A patent/BR112012032248A2/pt not_active Application Discontinuation
- 2011-06-17 CA CA2802541A patent/CA2802541A1/en not_active Abandoned
- 2011-06-17 CN CN201910082228.2A patent/CN109674753A/zh active Pending
- 2011-06-17 JP JP2013516636A patent/JP5847813B2/ja not_active Expired - Fee Related
- 2011-06-17 EP EP11728490.1A patent/EP2585048B1/en not_active Not-in-force
- 2011-06-17 ES ES11728490.1T patent/ES2676209T3/es active Active
- 2011-06-17 CN CN2011800283946A patent/CN103037843A/zh active Pending
- 2011-06-21 US US13/165,651 patent/US9241924B2/en active Active
-
2016
- 2016-01-21 US US15/002,498 patent/US10098843B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN109674753A (zh) | 2019-04-26 |
| CN103037843A (zh) | 2013-04-10 |
| EP2585048B1 (en) | 2018-04-11 |
| BR112012032248A2 (pt) | 2016-09-13 |
| JP5847813B2 (ja) | 2016-01-27 |
| JP2013529637A (ja) | 2013-07-22 |
| US10098843B2 (en) | 2018-10-16 |
| US9241924B2 (en) | 2016-01-26 |
| EP2585048A1 (en) | 2013-05-01 |
| US20160213618A1 (en) | 2016-07-28 |
| ES2676209T3 (es) | 2018-07-17 |
| US20110318418A1 (en) | 2011-12-29 |
| WO2011163090A1 (en) | 2011-12-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2585048B1 (en) | Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine | |
| EP2948141B1 (en) | Pharmaceutical composition with improved bioavailability | |
| RU2404775C2 (ru) | Фармацевтические композиции, содержащие иматиниб и замедлитель высвобождения | |
| JP4780522B2 (ja) | フェニルアラニン誘導体の固体分散体または固体分散体医薬製剤 | |
| EP3749301A1 (en) | Pharmaceutical compositions for treating cystic fibrosis | |
| WO2020242935A1 (en) | Methods of treatment for cystic fibrosis | |
| CA2877444C (en) | Pharmaceutical composition comprising fimasartan and hydrochlorothiazide | |
| ES2377552T3 (es) | Composiciones disueltas fácilmente y estables de candesartán cilexetilo preparadas con una granulación por vía húmeda | |
| EP2882424A1 (en) | Stable pharmaceutical composition containing 8-[(3r)-3-amino-1-piperidinyl]-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]-1h-purine-2,6-dione or a pharmaceutically acceptable salt thereof | |
| EP2618827A2 (en) | Antidiabetic solid pharmaceutical compositions | |
| WO2020225738A1 (en) | Pharmaceutical composition comprising venetoclax | |
| WO2017153939A1 (en) | Pharmaceutical composition comprising canagliflozin, process of preparation and use thereof | |
| WO2023227997A1 (en) | Pharmaceutical composition containing combination of azilsartan and chlorthalidone and process of preparation thereof | |
| HK1116067B (en) | Pharmaceutical compositions comprising imatinib and a release retardant |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20160616 |
|
| FZDE | Dead |
Effective date: 20201013 |