CA2586761A1 - Methods of treating diabetes mellitus - Google Patents
Methods of treating diabetes mellitus Download PDFInfo
- Publication number
- CA2586761A1 CA2586761A1 CA002586761A CA2586761A CA2586761A1 CA 2586761 A1 CA2586761 A1 CA 2586761A1 CA 002586761 A CA002586761 A CA 002586761A CA 2586761 A CA2586761 A CA 2586761A CA 2586761 A1 CA2586761 A1 CA 2586761A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- optionally substituted
- subject
- formula
- alkyl group
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 82
- 206010012601 diabetes mellitus Diseases 0.000 title abstract description 26
- 150000001875 compounds Chemical class 0.000 claims description 71
- -1 cyclic amine Chemical group 0.000 claims description 59
- 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 57
- 239000008103 glucose Substances 0.000 claims description 57
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 57
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 125000000623 heterocyclic group Chemical group 0.000 claims description 44
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 239000003814 drug Substances 0.000 claims description 38
- 210000004369 blood Anatomy 0.000 claims description 34
- 239000008280 blood Substances 0.000 claims description 34
- 102000004877 Insulin Human genes 0.000 claims description 29
- 108090001061 Insulin Proteins 0.000 claims description 29
- 229940125396 insulin Drugs 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 23
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 21
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 20
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
- 230000003247 decreasing effect Effects 0.000 claims description 15
- 102000017011 Glycated Hemoglobin A Human genes 0.000 claims description 13
- 239000003112 inhibitor Substances 0.000 claims description 13
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 108091005995 glycated hemoglobin Proteins 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 claims description 6
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 claims description 4
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- 229940100389 Sulfonylurea Drugs 0.000 claims description 3
- 230000007423 decrease Effects 0.000 claims description 3
- 239000012458 free base Substances 0.000 claims description 3
- 229960004580 glibenclamide Drugs 0.000 claims description 3
- 229960000698 nateglinide Drugs 0.000 claims description 3
- 229960002354 repaglinide Drugs 0.000 claims description 3
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 2
- 206010038468 Renal hypertrophy Diseases 0.000 claims description 2
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 2
- 206010020718 hyperplasia Diseases 0.000 claims description 2
- 201000008627 kidney hypertrophy Diseases 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 4
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 4
- 150000003892 tartrate salts Chemical group 0.000 claims 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 2
- 229910019142 PO4 Inorganic materials 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 claims 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims 2
- 229960003105 metformin Drugs 0.000 claims 2
- GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 2
- 239000010452 phosphate Substances 0.000 claims 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 2
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 claims 2
- 229960001641 troglitazone Drugs 0.000 claims 2
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 claims 2
- JEWKYOIHXAZUTF-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;hydrochloride Chemical compound Cl.OC(=O)C(O)C(O)C(O)=O JEWKYOIHXAZUTF-UHFFFAOYSA-N 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- 229940095064 tartrate Drugs 0.000 claims 1
- 239000003892 ceramide glucosyltransferase inhibitor Substances 0.000 abstract description 34
- 229940125921 glucosylceramide synthase inhibitor Drugs 0.000 abstract description 31
- 241000699670 Mus sp. Species 0.000 description 51
- 241000700159 Rattus Species 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- 125000003342 alkenyl group Chemical group 0.000 description 34
- 229940079593 drug Drugs 0.000 description 33
- PFJKOHUKELZMLE-VEUXDRLPSA-N ganglioside GM3 Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@@H]([C@H](O)/C=C/CCCCCCCCCCCCC)NC(=O)CCCCCCCCCCCCC\C=C/CCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O)[C@@H](CO)O1 PFJKOHUKELZMLE-VEUXDRLPSA-N 0.000 description 31
- 238000013293 zucker diabetic fatty rat Methods 0.000 description 31
- 125000000304 alkynyl group Chemical group 0.000 description 28
- 125000000753 cycloalkyl group Chemical group 0.000 description 23
- 150000002148 esters Chemical class 0.000 description 20
- 125000003368 amide group Chemical group 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 17
- 125000003545 alkoxy group Chemical group 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- 239000001257 hydrogen Substances 0.000 description 16
- 229910052739 hydrogen Inorganic materials 0.000 description 16
- 125000004149 thio group Chemical group *S* 0.000 description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 15
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 14
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 13
- 102100040247 Tumor necrosis factor Human genes 0.000 description 13
- 230000037396 body weight Effects 0.000 description 13
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 13
- 102000044956 Ceramide glucosyltransferases Human genes 0.000 description 12
- 108091000114 ceramide glucosyltransferase Proteins 0.000 description 12
- 125000004093 cyano group Chemical group *C#N 0.000 description 12
- 229960005335 propanol Drugs 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- 229910052736 halogen Inorganic materials 0.000 description 11
- 150000002367 halogens Chemical class 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 11
- 229940044613 1-propanol Drugs 0.000 description 10
- 102000003746 Insulin Receptor Human genes 0.000 description 10
- 108010001127 Insulin Receptor Proteins 0.000 description 10
- 206010022489 Insulin Resistance Diseases 0.000 description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 10
- 150000002339 glycosphingolipids Chemical class 0.000 description 10
- 238000003305 oral gavage Methods 0.000 description 10
- 125000003277 amino group Chemical group 0.000 description 9
- 125000001589 carboacyl group Chemical group 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 150000002305 glucosylceramides Chemical class 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 125000004043 oxo group Chemical group O=* 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 235000012631 food intake Nutrition 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 210000001789 adipocyte Anatomy 0.000 description 6
- 125000004104 aryloxy group Chemical group 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 125000001549 ceramide group Chemical group 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 230000000977 initiatory effect Effects 0.000 description 6
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 5
- 230000037406 food intake Effects 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 4
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 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 4
- 239000002775 capsule Substances 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 229940106189 ceramide Drugs 0.000 description 4
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 4
- IQZPDFORWZTSKT-UHFFFAOYSA-N nitrosulphonic acid Chemical compound OS(=O)(=O)[N+]([O-])=O IQZPDFORWZTSKT-UHFFFAOYSA-N 0.000 description 4
- 230000026731 phosphorylation Effects 0.000 description 4
- 238000006366 phosphorylation reaction Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 238000008157 ELISA kit Methods 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 230000036765 blood level Effects 0.000 description 3
- 150000001783 ceramides Chemical class 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 238000002651 drug therapy Methods 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 230000014101 glucose homeostasis Effects 0.000 description 3
- 238000007446 glucose tolerance test Methods 0.000 description 3
- 230000002440 hepatic effect Effects 0.000 description 3
- 235000009200 high fat diet Nutrition 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- BKMMTJMQCTUHRP-UHFFFAOYSA-N 2-aminopropan-1-ol Chemical group CC(N)CO BKMMTJMQCTUHRP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 208000015872 Gaucher disease Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WPIHMWBQRSAMDE-YCZTVTEBSA-N beta-D-galactosyl-(1->4)-beta-D-galactosyl-N-(pentacosanoyl)sphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO[C@@H]1O[C@H](CO)[C@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O)[C@H](O)\C=C\CCCCCCCCCCCCC WPIHMWBQRSAMDE-YCZTVTEBSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 230000004700 cellular uptake Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 150000002270 gangliosides Chemical class 0.000 description 2
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 2
- 230000005802 health problem Effects 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- SUFUKZSWUHZXAV-BTJKTKAUSA-N rosiglitazone maleate Chemical compound [H+].[H+].[O-]C(=O)\C=C/C([O-])=O.C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O SUFUKZSWUHZXAV-BTJKTKAUSA-N 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 150000003408 sphingolipids Chemical class 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
- 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 235000019489 Almond oil Nutrition 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
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical group NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 108010014663 Glycated Hemoglobin A Proteins 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 108010090613 Human Regular Insulin Proteins 0.000 description 1
- 102000013266 Human Regular Insulin Human genes 0.000 description 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102100030928 Lactosylceramide alpha-2,3-sialyltransferase Human genes 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 241000234435 Lilium Species 0.000 description 1
- 208000015439 Lysosomal storage disease Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- SQVRNKJHWKZAKO-LUWBGTNYSA-N N-acetylneuraminic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)CC(O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-LUWBGTNYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 108010005991 Pork Regular Insulin Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229940062328 actos Drugs 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000004171 alkoxy aryl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 229940000806 amaryl Drugs 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 125000005001 aminoaryl group Chemical group 0.000 description 1
- 125000004682 aminothiocarbonyl group Chemical group NC(=S)* 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229940054739 avandamet Drugs 0.000 description 1
- 229940062310 avandia Drugs 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical group C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- MYONAGGJKCJOBT-UHFFFAOYSA-N benzimidazol-2-one Chemical compound C1=CC=CC2=NC(=O)N=C21 MYONAGGJKCJOBT-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 125000004057 biotinyl group Chemical group [H]N1C(=O)N([H])[C@]2([H])[C@@]([H])(SC([H])([H])[C@]12[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000006790 cellular biosynthetic process Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 229940089126 diabeta Drugs 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 238000013229 diet-induced obese mouse Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 125000005303 dithiazolyl group Chemical group S1SNC(=C1)* 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical group O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
- 229940088991 glucotrol Drugs 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 229940120105 glynase Drugs 0.000 description 1
- 229940084937 glyset Drugs 0.000 description 1
- 108010076477 haematoside synthetase Proteins 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 229940103471 humulin Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
- 201000008980 hyperinsulinism Diseases 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 229910052816 inorganic phosphate Inorganic materials 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000013227 male C57BL/6J mice Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 229940103453 novolin Drugs 0.000 description 1
- 229940112879 novolog Drugs 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229940096058 prandin Drugs 0.000 description 1
- 210000000229 preadipocyte Anatomy 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 210000003314 quadriceps muscle Anatomy 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229940110862 starlix Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000006169 tetracyclic group Chemical group 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
- 229940035266 tolinase Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62644804P | 2004-11-10 | 2004-11-10 | |
| US60/626,448 | 2004-11-10 | ||
| PCT/US2005/040596 WO2006053043A2 (en) | 2004-11-10 | 2005-11-09 | Methods of treating diabetes mellitus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2586761A1 true CA2586761A1 (en) | 2006-05-18 |
Family
ID=35965895
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002586761A Pending CA2586761A1 (en) | 2004-11-10 | 2005-11-09 | Methods of treating diabetes mellitus |
Country Status (6)
| Country | Link |
|---|---|
| US (3) | US8003617B2 (https=) |
| EP (1) | EP1811991B1 (https=) |
| JP (4) | JP2008519840A (https=) |
| BR (1) | BRPI0517701A8 (https=) |
| CA (1) | CA2586761A1 (https=) |
| WO (1) | WO2006053043A2 (https=) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8003617B2 (en) | 2004-11-10 | 2011-08-23 | Genzyme Corporation | Methods of treating diabetes mellitus |
| PL2032134T3 (pl) * | 2006-05-09 | 2015-11-30 | Genzyme Corp | Sposoby leczenia stłuszczeniowej choroby wątroby obejmujące hamowanie syntezy glikosfingolipidów |
| US20100048714A1 (en) * | 2006-06-19 | 2010-02-25 | University Of Utah Research Foundation | Methods and Compositions Related to Inhibition of Ceramide Synthesis |
| EP2594562B1 (en) | 2007-05-31 | 2016-07-20 | Genzyme Corporation | 2-acylaminopropanol-type glucosylceramide synthase inhibitors |
| ES2660690T3 (es) | 2007-10-05 | 2018-03-23 | Genzyme Corporation | Método para tratar poliquistosis renales con derivados de ceramida |
| CA2731685A1 (en) * | 2008-07-28 | 2010-02-04 | Genzyme Corporation | Glucosylceramide synthase inhibition for the treatment of collapsing glomerulopathy and other glomerular disease |
| EP3078373A1 (en) | 2008-10-03 | 2016-10-12 | Genzyme Corporation | 2-acylaminopropanol-type glucosylceramide synthase inhibitor |
| WO2010091164A1 (en) | 2009-02-06 | 2010-08-12 | Exelixis, Inc. | Inhibitors of glucosylceramide synthase |
| WO2010091104A1 (en) | 2009-02-06 | 2010-08-12 | Exelixis, Inc. | Glucosylceramide synthase inhibitors |
| WO2011066352A1 (en) * | 2009-11-27 | 2011-06-03 | Genzyme Corporation | An amorphous and a crystalline form of genz 112638 hemitartrat as inhibitor of glucosylceramide synthase |
| AU2012231275A1 (en) | 2011-03-18 | 2013-10-17 | Genzyme Corporation | Glucosylceramide synthase inhibitors |
| WO2013078413A1 (en) * | 2011-11-22 | 2013-05-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Modulators of lipid storage |
| MA37975B2 (fr) | 2012-09-11 | 2021-03-31 | Genzyme Corp | Inhibiteurs de synthase de glucosylcéramide |
| TWI649317B (zh) | 2013-03-15 | 2019-02-01 | 健臻公司 | 製備葡糖基神經醯胺合成酶抑制劑之方法 |
| JO3713B1 (ar) | 2013-03-15 | 2021-01-31 | Genzyme Corp | أشكال ملح (s)-كوينوكليدين-3-يل(2-(2-(4-فلوروفينيل)ثيازول-4-يل)بروبان-2-يل)كارباميت |
| EP2968268B1 (en) | 2013-03-15 | 2020-07-29 | Concert Pharmaceuticals Inc. | Inhibitors of the enzyme udp-glucose: n-acyl-sphingosine glucosyltransferase |
| CN105745206B (zh) * | 2013-09-20 | 2019-08-13 | 生物马林药物股份有限公司 | 用于治疗疾病的葡萄糖神经酰胺合成酶抑制剂 |
| WO2015059679A1 (en) * | 2013-10-25 | 2015-04-30 | Dr. Reddy's Laboratories Limited | Improved process for the preparation of eliglustat |
| JP6526652B2 (ja) | 2013-10-29 | 2019-06-05 | ビオマリン プハルマセウトイカル インコーポレイテッド | グルコシルセラミドシンターゼ阻害剤としてのｎ−（１−ヒドロキシ−３−（ピロリジニル）プロパン−２−イル）ピロリジン−３−カルボキサミド誘導体 |
| US9758044B2 (en) * | 2014-10-02 | 2017-09-12 | Ford Global Technologies, Llc | Bus leakage resistance estimation for electrical isolation testing and diagnostics |
| KR101711706B1 (ko) * | 2014-11-20 | 2017-03-02 | 주식회사 엘지화학 | 공통 모드 노이즈 시뮬레이터 |
| CN107635980A (zh) | 2015-03-11 | 2018-01-26 | 生物马林药物股份有限公司 | 用于治疗疾病的葡糖神经酰胺合酶抑制剂 |
| WO2020026471A1 (ja) * | 2018-07-31 | 2020-02-06 | 株式会社親広産業 | グルコース消費促進剤および解糖系促進剤 |
| CN114040762A (zh) | 2019-02-04 | 2022-02-11 | 建新公司 | 使用葡糖神经酰胺合酶(gcs)的抑制剂治疗纤毛疾病 |
| CN114746422B (zh) | 2019-11-15 | 2024-03-12 | 柳韩洋行 | 具有1,2,3,4-四氢萘部分的衍生物或其药学上可接受的盐以及包含它们的药物组合物 |
| PL4041733T3 (pl) | 2019-11-15 | 2024-09-23 | Yuhan Corporation | Pochodne mające ugrupowanie 2,3-dihydro-1h-indenu lub 2,3-dihydrobenzofuranu lub ich farmaceutycznie dopuszczalne sole oraz kompozycje farmaceutyczne je zawierające |
| TW202142236A (zh) | 2020-02-03 | 2021-11-16 | 美商健臻公司 | 用於治療與溶體儲積症相關的神經症狀之方法 |
| KR20230043024A (ko) | 2020-07-24 | 2023-03-30 | 젠자임 코포레이션 | 벤글루스타트를 포함하는 제약 조성물 |
Family Cites Families (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1555654A (en) * | 1977-06-25 | 1979-11-14 | Exxon Research Engineering Co | Agricultural burner apparatus |
| US4065562A (en) * | 1975-12-29 | 1977-12-27 | Nippon Shinyaku Co., Ltd. | Method and composition for reducing blood glucose levels |
| NO154918C (no) * | 1977-08-27 | 1987-01-14 | Bayer Ag | Analogifremgangsmaate til fremstilling av terapeutisk aktive derivater av 3,4,5-trihydroksypiperidin. |
| GB2020278B (en) * | 1978-05-03 | 1983-02-23 | Nippon Shinyaku Co Ltd | Moranoline dervitives |
| JPS568318A (en) | 1979-06-28 | 1981-01-28 | Janssen Pharmaceutica Nv | Non oral long acting composition of haloperidol and bromperidol derivative |
| GB8311286D0 (en) | 1983-04-26 | 1983-06-02 | Searle & Co | Carboxyalkyl peptide derivatives |
| EP0144290A3 (de) | 1983-12-01 | 1987-05-27 | Ciba-Geigy Ag | Substituierte Aethylendiaminderivate |
| US5041441A (en) * | 1988-04-04 | 1991-08-20 | The Regents Of The University Of Michigan | Method of chemotherapy using 1-phenyl-2-decanoylamino-3-morpholino-1-propanol |
| JPH0416856A (ja) | 1990-05-10 | 1992-01-21 | Canon Inc | 正帯電性非磁性トナー |
| US5302609A (en) * | 1992-12-16 | 1994-04-12 | The Regents Of The University Of Michigan | Treatment of diabetic nephropathy |
| US5399567A (en) * | 1993-05-13 | 1995-03-21 | Monsanto Company | Method of treating cholera |
| CN1128951A (zh) * | 1993-08-13 | 1996-08-14 | 生化学工业株式会社 | 治疗神经元疾病的药物 |
| ES2149350T3 (es) * | 1994-02-02 | 2000-11-01 | Liposome Co Inc | Compuestos y liposomas farmaceuticamente activos y metodos para su utilizacion. |
| CN1152907A (zh) * | 1994-06-10 | 1997-06-25 | 生化学工业株式会社 | 2-酰胺基丙醇化合物及其药物组合物 |
| WO2001004108A1 (en) | 1999-07-09 | 2001-01-18 | Regents Of The University Of Michigan | Amino ceramide-like compounds and therapeutic methods of use |
| US20030073680A1 (en) * | 1995-09-20 | 2003-04-17 | The Regents Of The University Of Michigan | Amino ceramide-like compounds and therapeutic methods of use |
| WO1997010817A1 (en) * | 1995-09-20 | 1997-03-27 | The Regents Of The University Of Michigan | Amino ceramide-like compounds and therapeutic methods of use |
| US6890949B1 (en) * | 1999-07-09 | 2005-05-10 | The Regents Of The University Of Michigan | Amino ceramide-like compounds and therapeutic methods of use |
| US6255336B1 (en) * | 1995-09-20 | 2001-07-03 | The Regents Of The University Of Michigan | Amino ceramide-like compounds and therapeutic methods of use |
| NO965193L (no) * | 1995-12-08 | 1997-06-09 | Seikagaku Kogyo Kk Seikagaku C | Aminalkoholderivat og fremgangsmåte for fremstilling derav |
| JP3993908B2 (ja) | 1995-12-08 | 2007-10-17 | 生化学工業株式会社 | アミノアルコール誘導体及び該誘導体の製造方法 |
| JP4140984B2 (ja) | 1995-12-20 | 2008-08-27 | 生化学工業株式会社 | 分化誘導作用を有する薬剤 |
| US5972928A (en) | 1997-05-21 | 1999-10-26 | Johns Hopkins University | Methods for treatment of conditions associated with lactosylceramide |
| JP4036500B2 (ja) | 1997-05-23 | 2008-01-23 | 生化学工業株式会社 | アミノアルコール誘導体及びそれを含有する医薬 |
| JP4176170B2 (ja) | 1997-06-06 | 2008-11-05 | 生化学工業株式会社 | アミノアルコール誘導体を含む医薬及び異常増殖性疾患治療薬 |
| US6222619B1 (en) * | 1997-09-18 | 2001-04-24 | University Of Utah Research Foundation | Diagnostic device and method |
| US6465488B1 (en) * | 1997-12-11 | 2002-10-15 | Chancellor, Masters & Scholars Of The University Of Oxford | Inhibition of glycolipid biosynthesis |
| ATE358473T1 (de) * | 1998-07-27 | 2007-04-15 | Univ Johns Hopkins | Diamino-propanol-verbindungen zur behandlung von ischaemien |
| US6610703B1 (en) * | 1998-12-10 | 2003-08-26 | G.D. Searle & Co. | Method for treatment of glycolipid storage diseases |
| GB0100889D0 (en) | 2001-01-12 | 2001-02-21 | Oxford Glycosciences Uk Ltd | Compounds |
| JP2003521479A (ja) * | 1999-07-09 | 2003-07-15 | リージェンツ オブ ザ ユニバーシティ オブ ミシガン | アミノセラミド様化合物および治療目的での使用方法 |
| JP5009459B2 (ja) | 1999-12-06 | 2012-08-22 | 生化学工業株式会社 | アミノアルコール誘導体及びそれを含有する医薬 |
| US6407064B2 (en) | 1999-12-06 | 2002-06-18 | Seikagaku Corporation | Aminoalcohol derivative and medicament comprising the same |
| US6235737B1 (en) * | 2000-01-25 | 2001-05-22 | Peter Styczynski | Reduction of hair growth |
| NZ522036A (en) | 2000-04-19 | 2004-04-30 | Borody Thomas J | Compositions and therapies for hyperlipidaemia-associated disorders |
| CA2432908A1 (en) | 2000-12-20 | 2002-06-27 | Bristol-Myers Squibb Pharma Company | Diamines as modulators of chemokine receptor activity |
| JP2004523509A (ja) | 2000-12-29 | 2004-08-05 | ワイス | ベンゾ〔ｇ〕キノリン−３−カルボニトリルの置換体およびベンゾ〔ｇ〕キナゾリンの置換体の位置選択的調製方法 |
| US7148251B2 (en) * | 2001-01-10 | 2006-12-12 | The Regents Of The University Of Michigan | Amino ceramide-like compounds and therapeutic methods of use |
| US20020198240A1 (en) * | 2001-01-10 | 2002-12-26 | Shayman James A. | Amino ceramide - like compounds and therapeutic methods of use |
| BR0206400A (pt) * | 2001-01-10 | 2005-01-18 | Univ Michigan | Compostos de amino ceramidas e seus usos em métodos terapêuticos |
| US20040260099A1 (en) * | 2001-01-10 | 2004-12-23 | The Regents Of The University Of Michigan | Amino ceramide-like compounds and therapeutic methods of use |
| CA2453978C (en) | 2001-07-16 | 2011-10-11 | Genzyme Corporation | Synthesis of udp-glucose: n-acylsphingosine glucosyltransferase inhibitors |
| WO2003045928A1 (en) * | 2001-11-26 | 2003-06-05 | Genzyme Corporation | Diastereoselective synthesis of udp-glucose : n-acylsphingosine glucosyltransferase inhibitors |
| GB0229931D0 (en) * | 2002-12-21 | 2003-01-29 | Astrazeneca Ab | Therapeutic agents |
| AU2002367266A1 (en) * | 2001-12-28 | 2003-07-24 | Sumitomo Pharmaceuticals Company, Limited | Disease markers for renal diseaes and utilization thereof |
| ES2251677T3 (es) | 2002-01-22 | 2006-05-01 | Warner-Lambert Company Llc | 2-(piridin-2-ilamino)-pirido(2,3-d)pirimidin-7-onas. |
| EP1336411A1 (en) | 2002-02-14 | 2003-08-20 | Academisch Medisch Centrum bij de Universiteit van Amsterdam | Compositions and methods for improving enzyme replacement therapy of lysosomal storage diseases |
| JP2003238410A (ja) | 2002-02-21 | 2003-08-27 | Seibutsu Yuki Kagaku Kenkyusho:Kk | インスリン抵抗性解除剤 |
| US20060217560A1 (en) * | 2002-04-29 | 2006-09-28 | Shayman James A | Amino ceramide-like compounds and therapeutic methods of use |
| US6916802B2 (en) * | 2002-04-29 | 2005-07-12 | Genzyme Corporation | Amino ceramide-like compounds and therapeutic methods of use |
| AU2003246942B2 (en) | 2002-07-17 | 2009-06-25 | Idorsia Pharmaceuticals Ltd | Piperidinetriol derivatives as inhibitors of glycosylceramide synthase |
| RS20050035A (sr) | 2002-07-17 | 2007-06-04 | Biogen Idec Ma Inc., | Terapije bubrežne insuficijencije sa upotrebom interferona -beta |
| AU2003225670A1 (en) | 2003-02-28 | 2004-09-28 | Intermune, Inc. | Interferon drug therapy for the treatment of viral diseases and liver fibrosis |
| GB0313678D0 (en) * | 2003-06-13 | 2003-07-16 | Oxford Glycosciences Uk Ltd | Novel compounds |
| US7662838B2 (en) | 2003-10-29 | 2010-02-16 | Genzyme Corporation | Use of a deoxynojirimycin derivative or a pharmaceutically salt thereof |
| EP1528056A1 (en) | 2003-10-29 | 2005-05-04 | Academisch Ziekenhuis bij de Universiteit van Amsterdam | Deoxynojirimycin analogues and their uses as glucosylceramidase inhibitors |
| CA2548313A1 (en) | 2003-12-23 | 2005-07-14 | Musc Foundation For Research Development | Methods and compositions for the prevention and treatment of inflammatory diseases or conditions |
| GB0400812D0 (en) | 2004-01-14 | 2004-02-18 | Celltech R&D Ltd | Novel compounds |
| EP1576894A1 (en) * | 2004-03-16 | 2005-09-21 | Nederlandse Organisatie voor toegepast-natuurwetenschappelijk Onderzoek TNO | The use of sphingolipids in the treatment and prevention of type 2 diabetes mellitus, insulin resistance and Metabolic Syndrome |
| US20070207983A1 (en) * | 2004-03-16 | 2007-09-06 | Nieuwenhuizen Willem F | Use of Sphingolipids in the Treatment and Prevention of Type 2 Diabetes Mellitus, Insulin Resistance and Metabolic Syndrome |
| AU2005240714B2 (en) | 2004-05-07 | 2011-07-07 | Merck Patent Gmbh | GM3 synthase as a therapeutic target in microvascular complications of diabetes |
| WO2005123055A2 (en) | 2004-06-14 | 2005-12-29 | Musc Foundation For Research Development | Methods for treating inflammatory disorders |
| CA2581173A1 (en) * | 2004-08-20 | 2006-03-02 | The Johns Hopkins University | Methods for treatment of angiogenesis |
| US8003617B2 (en) | 2004-11-10 | 2011-08-23 | Genzyme Corporation | Methods of treating diabetes mellitus |
| ES2380904T3 (es) | 2005-01-26 | 2012-05-21 | Allergan, Inc. | Composiciones farmacéuticas que tienen un efecto analgésico y contienen 1-bencil-1-hidroxi-2,3-diamino-propil aminas, amidas del ácido 3-bencil-3-hidroxi-2-amino propiónico o compuestos relacionados |
| WO2007022518A2 (en) | 2005-08-19 | 2007-02-22 | Amylin Pharmaceuticals, Inc. | New uses of glucoregulatory proteins |
| PL2032134T3 (pl) | 2006-05-09 | 2015-11-30 | Genzyme Corp | Sposoby leczenia stłuszczeniowej choroby wątroby obejmujące hamowanie syntezy glikosfingolipidów |
| WO2008011478A2 (en) | 2006-07-19 | 2008-01-24 | Allergan, Inc. | Methods for treating chronic pain using 3-aryl-3-hydroxy-2-amino-propionic acid amides, 3-heteroaryl-3-hydroxy-2-amino-propionic acid amides and related compounds |
| WO2008011487A2 (en) | 2006-07-19 | 2008-01-24 | Allergan, Inc. | L-benzyl-l-hydr0xy-2, 3-diamin0-propyl amines and 3-benzyl-3-hydroxy-2-amino-propionicacid amides for chronic pain |
| GB0614947D0 (en) | 2006-07-27 | 2006-09-06 | Isis Innovation | Epitope reduction therapy |
| TWI389895B (zh) | 2006-08-21 | 2013-03-21 | Infinity Discovery Inc | 抑制ｂｃｌ蛋白質與結合夥伴間之交互作用的化合物及方法 |
| CN101646437A (zh) | 2007-02-09 | 2010-02-10 | Irm责任有限公司 | 作为通道活化蛋白酶抑制剂的化合物和组合物 |
| EP2594562B1 (en) | 2007-05-31 | 2016-07-20 | Genzyme Corporation | 2-acylaminopropanol-type glucosylceramide synthase inhibitors |
| ES2660690T3 (es) | 2007-10-05 | 2018-03-23 | Genzyme Corporation | Método para tratar poliquistosis renales con derivados de ceramida |
| WO2009117150A2 (en) | 2008-03-20 | 2009-09-24 | Genzyme Corporation | Method of treating lupus with ceramide derivatives |
| CA2731685A1 (en) | 2008-07-28 | 2010-02-04 | Genzyme Corporation | Glucosylceramide synthase inhibition for the treatment of collapsing glomerulopathy and other glomerular disease |
| EP3078373A1 (en) | 2008-10-03 | 2016-10-12 | Genzyme Corporation | 2-acylaminopropanol-type glucosylceramide synthase inhibitor |
-
2005
- 2005-11-09 US US11/667,224 patent/US8003617B2/en not_active Expired - Fee Related
- 2005-11-09 WO PCT/US2005/040596 patent/WO2006053043A2/en not_active Ceased
- 2005-11-09 BR BRPI0517701A patent/BRPI0517701A8/pt not_active Application Discontinuation
- 2005-11-09 JP JP2007541294A patent/JP2008519840A/ja not_active Withdrawn
- 2005-11-09 EP EP05826118.1A patent/EP1811991B1/en not_active Expired - Lifetime
- 2005-11-09 CA CA002586761A patent/CA2586761A1/en active Pending
-
2011
- 2011-07-29 US US13/193,990 patent/US20120022126A1/en not_active Abandoned
-
2012
- 2012-10-10 JP JP2012225142A patent/JP2013032377A/ja active Pending
-
2014
- 2014-07-28 JP JP2014152732A patent/JP5837657B2/ja not_active Expired - Fee Related
- 2014-08-20 US US14/464,432 patent/US9532976B2/en not_active Expired - Fee Related
-
2015
- 2015-07-03 JP JP2015134366A patent/JP2015193638A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006053043A3 (en) | 2006-08-24 |
| EP1811991B1 (en) | 2018-11-07 |
| US20080161379A1 (en) | 2008-07-03 |
| EP1811991A2 (en) | 2007-08-01 |
| JP2008519840A (ja) | 2008-06-12 |
| BRPI0517701A (pt) | 2008-10-21 |
| US20150190373A1 (en) | 2015-07-09 |
| US9532976B2 (en) | 2017-01-03 |
| JP5837657B2 (ja) | 2015-12-24 |
| US20120022126A1 (en) | 2012-01-26 |
| WO2006053043A2 (en) | 2006-05-18 |
| JP2014240402A (ja) | 2014-12-25 |
| US8003617B2 (en) | 2011-08-23 |
| JP2015193638A (ja) | 2015-11-05 |
| BRPI0517701A8 (pt) | 2018-01-23 |
| JP2013032377A (ja) | 2013-02-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9532976B2 (en) | Method of lowering blood glucose | |
| US6436938B1 (en) | Combination treatment for depression | |
| EP3132792B1 (en) | Composition and methods for increasing insulin sensitivity | |
| RU2581058C2 (ru) | Новые композиции для предупреждения и/или лечения дегенеративных расстройств центральной нервной системы | |
| CA2443031A1 (en) | Use of selective cox-2 inhibitors for the treatment of urinary incontinence | |
| KR20020073176A (ko) | 불안증 개선 방법 | |
| JP2010534668A (ja) | Ｉｒｓ−１及びａｋｔを活性化する方法 | |
| BRPI0615046B1 (pt) | uso de um composto | |
| JP2006519876A (ja) | 脂肪分解を誘発するためへの甲状腺刺激ホルモンの使用 | |
| ES2390053T3 (es) | Derivado de ácido fenilacético, procedimiento para producir el mismo y uso | |
| JP2008530198A (ja) | ４−ヒドロキシイソロイシンのジアステレオ異性体及びこれらの使用 | |
| AU723879B2 (en) | Combination therapy for the treatment of diabetes and obesity | |
| JP2001139491A (ja) | ａｐｏＢ分泌／ＭＴＰ阻害剤及び抗肥満剤の使用 | |
| WO2005009471A1 (en) | Composition for lowering blood-sugar level | |
| JP2000500490A (ja) | 糖尿病治療用の４−ヒドロキシクマリン−３−カルボキシアミド | |
| CN108969512A (zh) | 一种r-氟西汀或外消旋氟西汀盐型的药物组合物及其用途 | |
| CN115087643B (zh) | 稠和杂环类化合物及其制备方法和医药用途 | |
| US20250302823A1 (en) | Compositions and methods for treating hepatic porphyrias with glycine transport inhibitors | |
| CN101801373A (zh) | 具有抗糖尿病作用的药物组合物 | |
| AU2003262286B2 (en) | Novel Effectors of Dipeptidyl Peptidase IV | |
| Mulani | Effect Of Topiramate On Body Weight, Systolic Blood Pressure And Spontaneous Motor Activity In Olanzapine Treated Rats | |
| HK1235628A1 (en) | Novel compositions for preventing and/or treating degenerative disorders of the central nervous system | |
| NZ623571A (en) | Dosage regimen for an s1p receptor modulator or agonist | |
| AU2006202684A1 (en) | Novel effectors of dipeptidyl peptidase IV |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |