JP4754487B2 - グルカゴン様ペプチド（ｇｌｐ）−１化合物またはメラノコルチン４受容体（ｍｃ４）アゴニストペプチドの経口デリバリーのための化合物、方法および製剤 - Google Patents
グルカゴン様ペプチド（ｇｌｐ）−１化合物またはメラノコルチン４受容体（ｍｃ４）アゴニストペプチドの経口デリバリーのための化合物、方法および製剤 Download PDFInfo
- Publication number
- JP4754487B2 JP4754487B2 JP2006523866A JP2006523866A JP4754487B2 JP 4754487 B2 JP4754487 B2 JP 4754487B2 JP 2006523866 A JP2006523866 A JP 2006523866A JP 2006523866 A JP2006523866 A JP 2006523866A JP 4754487 B2 JP4754487 B2 JP 4754487B2
- Authority
- JP
- Japan
- Prior art keywords
- glp
- compounds
- compound
- delivery
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 31
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 22
- 239000000556 agonist Substances 0.000 title claims description 13
- 239000000203 mixture Substances 0.000 title abstract description 34
- 238000009472 formulation Methods 0.000 title abstract description 19
- 238000000034 method Methods 0.000 title abstract description 7
- 102000001796 Melanocortin 4 receptors Human genes 0.000 title abstract 3
- 108010021436 Type 4 Melanocortin Receptor Proteins 0.000 title abstract 3
- 102000004196 processed proteins & peptides Human genes 0.000 title description 6
- 108010088406 Glucagon-Like Peptides Proteins 0.000 title 2
- -1 glucagon like peptide-1 compound Chemical class 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 229960001639 penicillamine Drugs 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 102100025101 GATA-type zinc finger protein 1 Human genes 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 abstract 1
- 102100040918 Pro-glucagon Human genes 0.000 abstract 1
- 239000000018 receptor agonist Substances 0.000 abstract 1
- 229940044601 receptor agonist Drugs 0.000 abstract 1
- 239000013543 active substance Substances 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000000126 substance Substances 0.000 description 21
- 239000002904 solvent Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 11
- 239000000284 extract Substances 0.000 description 10
- 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 9
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 6
- 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 6
- 239000000463 material Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 241001465754 Metazoa Species 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
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 210000001105 femoral artery Anatomy 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 229920000669 heparin Polymers 0.000 description 3
- 229960002897 heparin Drugs 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- FBNPZXIJGJBWOX-UHFFFAOYSA-N methyl 6-oxo-6-[2-(pyridine-2-carbonyl)hydrazinyl]hexanoate Chemical compound COC(=O)CCCCC(=O)NNC(=O)C1=CC=CC=N1 FBNPZXIJGJBWOX-UHFFFAOYSA-N 0.000 description 3
- 239000004005 microsphere Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- BPHJHAJXWGKPAC-UHFFFAOYSA-N 2-(1-ethoxyethenyl)-3-methoxypyridine Chemical compound CCOC(=C)C1=NC=CC=C1OC BPHJHAJXWGKPAC-UHFFFAOYSA-N 0.000 description 2
- PDOWLYNSFYZIQX-UHFFFAOYSA-N 2-bromo-3-methoxypyridine Chemical compound COC1=CC=CN=C1Br PDOWLYNSFYZIQX-UHFFFAOYSA-N 0.000 description 2
- PJMGKFDGAQKPKW-UHFFFAOYSA-N 2-methyl-5-(4-thiophen-3-yl-1,3-oxazol-2-yl)pentanoic acid Chemical compound CC(CCCC1=NC(=CO1)C2=CSC=C2)C(=O)O PJMGKFDGAQKPKW-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
- 101000978418 Homo sapiens Melanocortin receptor 4 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 102100023724 Melanocortin receptor 4 Human genes 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000011149 active material Substances 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 229940124447 delivery agent Drugs 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 238000010829 isocratic elution Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- HLPLFRJHZAUVIE-UHFFFAOYSA-N methyl 5-(5-pyridin-2-yl-1,3,4-oxadiazol-2-yl)pentanoate Chemical compound O1C(CCCCC(=O)OC)=NN=C1C1=CC=CC=N1 HLPLFRJHZAUVIE-UHFFFAOYSA-N 0.000 description 2
- HNBDRPTVWVGKBR-UHFFFAOYSA-N methyl pentanoate Chemical compound CCCCC(=O)OC HNBDRPTVWVGKBR-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 1
- ZNEMGFATAVGQSF-UHFFFAOYSA-N 1-(2-amino-6,7-dihydro-4H-[1,3]thiazolo[4,5-c]pyridin-5-yl)-2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]ethanone Chemical compound NC=1SC2=C(CN(CC2)C(CC=2OC(=NN=2)C=2C=NC(=NC=2)NC2CC3=CC=CC=C3C2)=O)N=1 ZNEMGFATAVGQSF-UHFFFAOYSA-N 0.000 description 1
- CYANWVCVJQOGOK-UHFFFAOYSA-N 2-bromo-1-(3-methoxypyridin-2-yl)ethanone Chemical compound COC1=CC=CN=C1C(=O)CBr CYANWVCVJQOGOK-UHFFFAOYSA-N 0.000 description 1
- TXEJYUFJFSPCHH-UHFFFAOYSA-N 2-bromo-1-thiophen-3-ylethanone Chemical compound BrCC(=O)C=1C=CSC=1 TXEJYUFJFSPCHH-UHFFFAOYSA-N 0.000 description 1
- YKHQFTANTNMYPP-UHFFFAOYSA-N 2-bromopyridin-3-ol Chemical compound OC1=CC=CN=C1Br YKHQFTANTNMYPP-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- DUPKBGJFDVFTFA-UHFFFAOYSA-N 5-(5-pyridin-2-yl-1,3,4-oxadiazol-2-yl)pentanoic acid Chemical compound O1C(CCCCC(=O)O)=NN=C1C1=CC=CC=N1 DUPKBGJFDVFTFA-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- UAZMGDIQVWZZHG-UHFFFAOYSA-N 8-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)octanoic acid Chemical compound O1C(CCCCCCCC(=O)O)=NC(C=2N=CC=CC=2)=N1 UAZMGDIQVWZZHG-UHFFFAOYSA-N 0.000 description 1
- KOVPXZDUVJGGFU-UHFFFAOYSA-N 8-methoxy-8-oxooctanoic acid Chemical compound COC(=O)CCCCCCC(O)=O KOVPXZDUVJGGFU-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 1
- LGBAPHKRXDPFTJ-UHFFFAOYSA-N COC(CCCCC(OCC(c1c[s]cc1)=O)=O)=O Chemical compound COC(CCCCC(OCC(c1c[s]cc1)=O)=O)=O LGBAPHKRXDPFTJ-UHFFFAOYSA-N 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 206010012186 Delayed delivery Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108010011459 Exenatide Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 1
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 1
- 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 229920001499 Heparinoid Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- WDNQVCITCZIOTK-UHFFFAOYSA-N OC(CCCCc1nc(-c([s]cc2)c2O)c[o]1)=O Chemical compound OC(CCCCc1nc(-c([s]cc2)c2O)c[o]1)=O WDNQVCITCZIOTK-UHFFFAOYSA-N 0.000 description 1
- USLYDPDUBZHXON-UHFFFAOYSA-N OC(CCCCc1nc(-c2ccc[s]2)c[o]1)=O Chemical compound OC(CCCCc1nc(-c2ccc[s]2)c[o]1)=O USLYDPDUBZHXON-UHFFFAOYSA-N 0.000 description 1
- QODKEDJYPOOUSG-UHFFFAOYSA-N OC(CCCCc1nc(-c2ccccn2)c[o]1)=O Chemical compound OC(CCCCc1nc(-c2ccccn2)c[o]1)=O QODKEDJYPOOUSG-UHFFFAOYSA-N 0.000 description 1
- RQCOPZAHZXHYCP-UHFFFAOYSA-N OC(CCCCc1nc(-c2ccncc2)c[o]1)=O Chemical compound OC(CCCCc1nc(-c2ccncc2)c[o]1)=O RQCOPZAHZXHYCP-UHFFFAOYSA-N 0.000 description 1
- SBHMXQCJPZTDRX-UHFFFAOYSA-N OC(CCCCc1nc(-c2cnccc2)c[o]1)=O Chemical compound OC(CCCCc1nc(-c2cnccc2)c[o]1)=O SBHMXQCJPZTDRX-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101710126321 Pancreatic trypsin inhibitor Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000012455 bioassay technique Methods 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=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](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)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)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 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
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- MUCZHBLJLSDCSD-UHFFFAOYSA-N diisopropyl fluorophosphate Chemical compound CC(C)OP(F)(=O)OC(C)C MUCZHBLJLSDCSD-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- ADPAQMFMDYVWKL-UHFFFAOYSA-N ethyl 8-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)octanoate Chemical compound O1C(CCCCCCCC(=O)OCC)=NC(C=2N=CC=CC=2)=N1 ADPAQMFMDYVWKL-UHFFFAOYSA-N 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 108010015174 exendin 3 Proteins 0.000 description 1
- LMHMJYMCGJNXRS-IOPUOMRJSA-N exendin-3 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=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](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)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](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@H](C)O)[C@H](C)O)C(C)C)C1=CC=CC=C1 LMHMJYMCGJNXRS-IOPUOMRJSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 239000003269 fluorescent indicator Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229960005051 fluostigmine Drugs 0.000 description 1
- 230000005251 gamma ray Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000002554 heparinoid Substances 0.000 description 1
- 229940025770 heparinoids Drugs 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- PSHNBYJXNBSZHI-UHFFFAOYSA-N methyl 6-amino-6-oxohexanoate Chemical compound COC(=O)CCCCC(N)=O PSHNBYJXNBSZHI-UHFFFAOYSA-N 0.000 description 1
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 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(=O)NCC(O)=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 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- BAQLNPIEFOYKNB-UHFFFAOYSA-N pyridine-2-carbohydrazide Chemical compound NNC(=O)C1=CC=CC=N1 BAQLNPIEFOYKNB-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 229920003987 resole Polymers 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000011123 type I (borosilicate glass) Substances 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49653703P | 2003-08-20 | 2003-08-20 | |
| US60/496,537 | 2003-08-20 | ||
| PCT/US2004/024387 WO2005019212A1 (en) | 2003-08-20 | 2004-08-18 | Compounds, methods and formulations for the oral delivery of a glucagon like peptide (glp)-1 compound or an melanocortin 4 receptor (mc4) agonist peptide |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007502817A JP2007502817A (ja) | 2007-02-15 |
| JP2007502817A5 JP2007502817A5 (https=) | 2007-05-31 |
| JP4754487B2 true JP4754487B2 (ja) | 2011-08-24 |
Family
ID=34216017
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006523866A Expired - Fee Related JP4754487B2 (ja) | 2003-08-20 | 2004-08-18 | グルカゴン様ペプチド（ｇｌｐ）−１化合物またはメラノコルチン４受容体（ｍｃ４）アゴニストペプチドの経口デリバリーのための化合物、方法および製剤 |
| JP2011104435A Pending JP2011207886A (ja) | 2003-08-20 | 2011-05-09 | グルカゴン様ペプチド（ｇｌｐ）−１化合物またはメラノコルチン４受容体（ｍｃ４）アゴニストペプチドの経口デリバリーのための化合物、方法および製剤 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011104435A Pending JP2011207886A (ja) | 2003-08-20 | 2011-05-09 | グルカゴン様ペプチド（ｇｌｐ）−１化合物またはメラノコルチン４受容体（ｍｃ４）アゴニストペプチドの経口デリバリーのための化合物、方法および製剤 |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US20070293423A1 (https=) |
| EP (1) | EP1658285B1 (https=) |
| JP (2) | JP4754487B2 (https=) |
| CN (1) | CN100398536C (https=) |
| AT (1) | ATE361294T1 (https=) |
| AU (1) | AU2004267044B8 (https=) |
| BR (1) | BRPI0413676B8 (https=) |
| CA (1) | CA2530983C (https=) |
| DE (1) | DE602004006279T2 (https=) |
| ES (1) | ES2286679T3 (https=) |
| MX (1) | MXPA06001916A (https=) |
| WO (1) | WO2005019212A1 (https=) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009500426A (ja) | 2005-07-08 | 2009-01-08 | ソシエテ・ドゥ・コンセイユ・ドゥ・ルシェルシュ・エ・ダプリカーション・シャンティフィック・エス・ア・エス | メラノコルチン受容体のリガンド |
| NZ565217A (en) | 2005-07-08 | 2010-03-26 | Ipsen Pharma Sas | Melanocortin receptor ligands |
| JP5577094B2 (ja) * | 2006-08-31 | 2014-08-20 | エミスフェアー・テクノロジーズ・インク | 活性薬剤を送達するための化合物及び組成物 |
| TWI364290B (en) * | 2007-05-25 | 2012-05-21 | Ipsen Pharma Sas | Melanocortin receptor ligands modifled with hydantoin |
| KR101687037B1 (ko) * | 2008-06-09 | 2016-12-15 | 팔라틴 테크놀로지스 인코포레이티드 | 성기능 장애 치료용 멜라노코르틴 수용체-특이적 펩티드 |
| EP2440572B1 (en) | 2009-06-08 | 2017-04-05 | Palatin Technologies, Inc. | Lactam-bridged melanocortin receptor-specific peptides |
| UY32690A (es) | 2009-06-08 | 2011-01-31 | Astrazeneca Ab | Péptidos específicos para receptores de melanocortina |
| CA2761607C (en) | 2009-06-08 | 2018-09-04 | Yi-Qun Shi | Melanocortin receptor-specific peptides |
| BR112012011780A2 (pt) | 2009-11-23 | 2019-09-24 | Palatin Technologies, Inc | peptídeo linear,composição farmacêutica,métodopara tratamento de umadoença,indicação,condição ou sídrome mediadsa por receptor de melanocortina emum mamífero humano ou não humano e método para tratamento de uma condição responsiva ás alterações em função de receptor de melanocortina em um mamifero humano ou não humano |
| JP5999702B2 (ja) | 2009-11-23 | 2016-09-28 | パラティン テクノロジーズ, インコーポレイテッドPalatin Technologies, Inc. | メラノコルチン−１受容体特異的環状ペプチド |
| US10357348B2 (en) * | 2013-08-19 | 2019-07-23 | Warren Matthew Leevy | Fluid manifold |
| US20160244860A1 (en) * | 2015-02-20 | 2016-08-25 | Cytec Industries Inc. | Aliphatic-aromatic heterocyclic compounds and uses thereof in metal extractant compositions |
| WO2016168388A2 (en) | 2015-04-14 | 2016-10-20 | Palatin Technologies, Inc. | Therapies for obesity, diabetes and related indications |
| CN105017136A (zh) * | 2015-07-24 | 2015-11-04 | 陈吉美 | 一种2-溴-3-甲氧基吡啶的制备方法 |
| BR112019016241A2 (pt) | 2017-02-08 | 2020-04-07 | Bayer Cropscience Ag | derivados de triazol e seu uso como fungicidas |
| EA201991839A1 (ru) | 2017-02-08 | 2020-02-17 | Байер Акциенгезельшафт | Новые производные триазолтиона |
| WO2018145934A1 (en) | 2017-02-08 | 2018-08-16 | Bayer Cropscience Aktiengesellschaft | Novel triazole derivatives |
| CA3052898A1 (en) | 2017-02-10 | 2018-08-16 | Bayer Aktiengesellschaft | Composition for controlling harmful microorganisms comprising 1 -(phenoxy-pyridinyl)-2-(1,2,4-triazol-1 -yl)-ethanol derivatives |
| WO2020020816A1 (en) | 2018-07-26 | 2020-01-30 | Bayer Aktiengesellschaft | Novel triazole derivatives |
| CN111793038B (zh) * | 2019-04-08 | 2022-08-12 | 新发药业有限公司 | 一种取代噁唑化合物的环保制备方法 |
| WO2025158275A1 (en) | 2024-01-24 | 2025-07-31 | Pfizer Inc. | Combination therapy using glucose-dependent insulinotropic polypeptide receptor antagonist compounds and glp-1 receptor agonist compounds |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1129393A (en) * | 1965-12-13 | 1968-10-02 | Miles Lab | Tetrazolyl alkanoic acids |
| JPH04234857A (ja) * | 1990-04-12 | 1992-08-24 | Hoechst Ag | ３，５−ジ置換２−イソキサゾリンおよびイソキサゾール、それらの製法およびそれらを含有する薬学的組成物 |
| JPH1160571A (ja) * | 1996-07-19 | 1999-03-02 | Takeda Chem Ind Ltd | 複素環化合物、その製造法および用途 |
| WO2002050091A1 (en) * | 2000-12-21 | 2002-06-27 | Glaxo Group Limited | Macrolide antibiotics |
| JP2002212171A (ja) * | 2000-11-17 | 2002-07-31 | Takeda Chem Ind Ltd | イソオキサゾール誘導体 |
| WO2002064607A1 (fr) * | 2001-02-14 | 2002-08-22 | Meiji Seika Kaisha, Ltd. | Nouveaux derives de macrolides a 16 elements modifies en 12 et 13 |
| GB2373186A (en) * | 2001-02-23 | 2002-09-18 | Astrazeneca Ab | Pharmaceutical combinations of a CCR3 antagonist and a compound which is usefulreatment of asthma, allergic disease or inflammation |
| WO2002096359A2 (en) * | 2001-05-30 | 2002-12-05 | Merck & Co., Inc. | Piperazine pentanamide hiv protease inhibitors |
| JP2003507456A (ja) * | 1999-08-24 | 2003-02-25 | アストラゼネカ ユーケイ リミテッド | ケモカインレセプター活性のモジュレーターとして有用な置換ピペリジン化合物 |
| WO2003015785A1 (en) * | 2001-08-15 | 2003-02-27 | Icos Corporation | 2h-phthalazin-1-ones and methods for use thereof |
| WO2003057215A1 (en) * | 2001-12-28 | 2003-07-17 | Takeda Chemical Industries, Ltd. | Neurotrophic factor production/secretion accelerator |
| JP2004277397A (ja) * | 2002-05-24 | 2004-10-07 | Takeda Chem Ind Ltd | １，２−アゾール誘導体 |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2423709A (en) * | 1947-07-08 | X-aryl thiazole | ||
| US595503A (en) * | 1897-12-14 | Cross-clevis | ||
| US3578671A (en) * | 1967-11-06 | 1971-05-11 | Wyeth John & Brother Ltd | Oxazoles |
| FR2374910A1 (fr) * | 1976-10-23 | 1978-07-21 | Choay Sa | Preparation a base d'heparine, comprenant des liposomes, procede pour l'obtenir et medicaments contenant de telles preparations |
| AU610083B2 (en) * | 1986-08-18 | 1991-05-16 | Clinical Technologies Associates, Inc. | Delivery systems for pharmacological agents |
| US5693338A (en) * | 1994-09-29 | 1997-12-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
| US5541155A (en) * | 1994-04-22 | 1996-07-30 | Emisphere Technologies, Inc. | Acids and acid salts and their use in delivery systems |
| US5643957A (en) * | 1993-04-22 | 1997-07-01 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| CN1151836C (zh) * | 1995-03-31 | 2004-06-02 | 艾米斯菲尔技术有限公司 | 用作传送活性剂的化合物和组合物 |
| US5866536A (en) * | 1995-03-31 | 1999-02-02 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5989539A (en) * | 1995-03-31 | 1999-11-23 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5965121A (en) * | 1995-03-31 | 1999-10-12 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5650386A (en) * | 1995-03-31 | 1997-07-22 | Emisphere Technologies, Inc. | Compositions for oral delivery of active agents |
| US6001347A (en) * | 1995-03-31 | 1999-12-14 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5820881A (en) * | 1995-04-28 | 1998-10-13 | Emisphere Technologies, Inc. | Microspheres of diamide-dicarboxylic acids |
| GB9604242D0 (en) * | 1996-02-28 | 1996-05-01 | Glaxo Wellcome Inc | Chemical compounds |
| US6211215B1 (en) * | 1996-07-19 | 2001-04-03 | Takeda Chemical Industries, Ltd. | Heterocyclic compounds, their production and use |
| US6313088B1 (en) * | 1997-02-07 | 2001-11-06 | Emisphere Technologies, Inc. | 8-[(2-hydroxy-4-methoxy benzoyl) amino]-octanoic acid compositions for delivering active agents |
| ATE383169T1 (de) * | 1997-02-07 | 2008-01-15 | Emisphere Tech Inc | Komponente und zusammensetzungen zur verabreichung von wirkstoffen |
| JP2002534363A (ja) | 1999-01-08 | 2002-10-15 | エミスフェアー・テクノロジーズ・インク | ポリマー性デリバリー剤及びデリバリー剤化合物 |
| ES2251976T3 (es) * | 1999-02-11 | 2006-05-16 | Emisphere Technologies, Inc. | Compuestos y composiciones de oxadiazol para aportar agentes activos. |
| MXPA01008611A (es) | 1999-02-26 | 2003-06-24 | Emisphere Tech Inc | Compuestos y composiciones para suministrar agentes activos. |
| ES2235854T3 (es) | 1999-04-05 | 2005-07-16 | Emisphere Technologies, Inc. | Sales disodicas, monohidratos y solvatos etanolicos para aportar agentes activos. |
| AR035016A1 (es) * | 1999-08-25 | 2004-04-14 | Takeda Chemical Industries Ltd | Composicion de azol promotor de produccion/secrecion de neurotrofina, compuesto prodroga del mismo, composicion farmaceutica que lo comprende y uso del mismo para preparar esta ultima. |
| MXPA02004092A (es) | 1999-11-05 | 2003-02-12 | Emisphere Tech Inc | Compuestos y composiciones de acido fenilaminocarboxilico para administrar agentes activos. |
| ES2298168T3 (es) | 1999-12-16 | 2008-05-16 | Emisphere Technologies, Inc. | Compuestos y composiciones para suministrar agentes activos. |
| US7151191B2 (en) | 2000-01-13 | 2006-12-19 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| ES2306719T3 (es) | 2000-06-29 | 2008-11-16 | Emisphere Technologies, Inc. | Compuestos y composiciones para la administracion de principios activos. |
| JP2004509084A (ja) * | 2000-08-23 | 2004-03-25 | イーライ・リリー・アンド・カンパニー | オキサゾリル−アリールオキシ酢酸誘導体およびそのｐｐａｒアゴニストとしての使用 |
| CA2418104A1 (en) * | 2000-08-23 | 2002-02-28 | Eli Lilly And Company | Oxazolyl-arylpropionic acid derivatives and their use as ppar agonists |
| EP1340749A4 (en) * | 2000-11-17 | 2007-09-05 | Takeda Pharmaceutical | ISOXAZOLE DERIVATIVES |
| US6969057B2 (en) | 2001-10-30 | 2005-11-29 | Illinois Tool Works Inc. | Method and apparatus for adjusting and positioning air caps |
| PL209734B1 (pl) | 2002-02-20 | 2011-10-31 | Emisphere Tech Inc | Preparat farmaceutyczny zawierający związek GLP-1 i czynnik dostarczający oraz jego zastosowanie |
| US20060148858A1 (en) * | 2002-05-24 | 2006-07-06 | Tsuyoshi Maekawa | 1, 2-Azole derivatives with hypoglycemic and hypolipidemic activity |
| EP1644023A2 (en) | 2003-06-19 | 2006-04-12 | Eli Lilly And Company | Melanocortin recptor 4(mc4) agonists and their uses |
| ATE350369T1 (de) * | 2003-08-20 | 2007-01-15 | Lilly Co Eli | Verbindungen, verfahren und formulierungen zur oralen verabreichung einer glucagon like peptide (glp)-1-verbindung oder eines am melanocortin-4- rezeptor (mc4) als agonist wirkenden peptids |
-
2004
- 2004-08-18 EP EP04779447A patent/EP1658285B1/en not_active Expired - Lifetime
- 2004-08-18 AT AT04779447T patent/ATE361294T1/de not_active IP Right Cessation
- 2004-08-18 BR BRPI0413676A patent/BRPI0413676B8/pt not_active IP Right Cessation
- 2004-08-18 DE DE602004006279T patent/DE602004006279T2/de not_active Expired - Lifetime
- 2004-08-18 JP JP2006523866A patent/JP4754487B2/ja not_active Expired - Fee Related
- 2004-08-18 WO PCT/US2004/024387 patent/WO2005019212A1/en not_active Ceased
- 2004-08-18 CA CA2530983A patent/CA2530983C/en not_active Expired - Fee Related
- 2004-08-18 US US10/566,012 patent/US20070293423A1/en not_active Abandoned
- 2004-08-18 MX MXPA06001916A patent/MXPA06001916A/es active IP Right Grant
- 2004-08-18 CN CNB2004800227912A patent/CN100398536C/zh not_active Expired - Fee Related
- 2004-08-18 ES ES04779447T patent/ES2286679T3/es not_active Expired - Lifetime
- 2004-08-18 AU AU2004267044A patent/AU2004267044B8/en not_active Ceased
-
2008
- 2008-11-03 US US12/263,722 patent/US7947841B2/en not_active Expired - Fee Related
-
2011
- 2011-04-14 US US13/087,255 patent/US8546581B2/en not_active Expired - Fee Related
- 2011-05-09 JP JP2011104435A patent/JP2011207886A/ja active Pending
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1129393A (en) * | 1965-12-13 | 1968-10-02 | Miles Lab | Tetrazolyl alkanoic acids |
| JPH04234857A (ja) * | 1990-04-12 | 1992-08-24 | Hoechst Ag | ３，５−ジ置換２−イソキサゾリンおよびイソキサゾール、それらの製法およびそれらを含有する薬学的組成物 |
| JPH1160571A (ja) * | 1996-07-19 | 1999-03-02 | Takeda Chem Ind Ltd | 複素環化合物、その製造法および用途 |
| JP2003507456A (ja) * | 1999-08-24 | 2003-02-25 | アストラゼネカ ユーケイ リミテッド | ケモカインレセプター活性のモジュレーターとして有用な置換ピペリジン化合物 |
| JP2002212171A (ja) * | 2000-11-17 | 2002-07-31 | Takeda Chem Ind Ltd | イソオキサゾール誘導体 |
| WO2002050091A1 (en) * | 2000-12-21 | 2002-06-27 | Glaxo Group Limited | Macrolide antibiotics |
| WO2002064607A1 (fr) * | 2001-02-14 | 2002-08-22 | Meiji Seika Kaisha, Ltd. | Nouveaux derives de macrolides a 16 elements modifies en 12 et 13 |
| GB2373186A (en) * | 2001-02-23 | 2002-09-18 | Astrazeneca Ab | Pharmaceutical combinations of a CCR3 antagonist and a compound which is usefulreatment of asthma, allergic disease or inflammation |
| WO2002096359A2 (en) * | 2001-05-30 | 2002-12-05 | Merck & Co., Inc. | Piperazine pentanamide hiv protease inhibitors |
| WO2003015785A1 (en) * | 2001-08-15 | 2003-02-27 | Icos Corporation | 2h-phthalazin-1-ones and methods for use thereof |
| WO2003057215A1 (en) * | 2001-12-28 | 2003-07-17 | Takeda Chemical Industries, Ltd. | Neurotrophic factor production/secretion accelerator |
| JP2004277397A (ja) * | 2002-05-24 | 2004-10-07 | Takeda Chem Ind Ltd | １，２−アゾール誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2286679T3 (es) | 2007-12-01 |
| DE602004006279D1 (de) | 2007-06-14 |
| MXPA06001916A (es) | 2006-05-17 |
| US20110190205A1 (en) | 2011-08-04 |
| JP2011207886A (ja) | 2011-10-20 |
| AU2004267044A1 (en) | 2005-03-03 |
| EP1658285A1 (en) | 2006-05-24 |
| AU2004267044B8 (en) | 2009-12-17 |
| WO2005019212A1 (en) | 2005-03-03 |
| CN1832944A (zh) | 2006-09-13 |
| US20070293423A1 (en) | 2007-12-20 |
| JP2007502817A (ja) | 2007-02-15 |
| CA2530983C (en) | 2012-09-25 |
| ATE361294T1 (de) | 2007-05-15 |
| BRPI0413676B8 (pt) | 2021-05-25 |
| EP1658285B1 (en) | 2007-05-02 |
| CA2530983A1 (en) | 2005-03-03 |
| US20090239798A1 (en) | 2009-09-24 |
| AU2004267044B2 (en) | 2009-12-03 |
| BRPI0413676B1 (pt) | 2018-07-24 |
| US7947841B2 (en) | 2011-05-24 |
| DE602004006279T2 (de) | 2007-12-27 |
| BRPI0413676A (pt) | 2006-10-24 |
| US8546581B2 (en) | 2013-10-01 |
| CN100398536C (zh) | 2008-07-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4754487B2 (ja) | グルカゴン様ペプチド（ｇｌｐ）−１化合物またはメラノコルチン４受容体（ｍｃ４）アゴニストペプチドの経口デリバリーのための化合物、方法および製剤 | |
| JP7581192B2 (ja) | アンドロゲン受容体モジュレーター及びその使用方法 | |
| KR101724161B1 (ko) | 세포내 칼슘을 조절하는 화합물 | |
| CN1923820B (zh) | 新的羧酸衍生物，其制备和应用 | |
| US8765796B2 (en) | Compounds, methods and formulations for the oral delivery of a glucagon-like peptide (GLP-1) compound or a melanocortin-4 receptor (MC4) agonist peptide | |
| KR20220004978A (ko) | 단백질 분해 표적 키메라 리간드로서 사용하기 위한 안드로겐 수용체 조절제 및 방법 | |
| CN1253553A (zh) | 取代的苯基衍生物、其制备方法以及用途 | |
| US20100274022A1 (en) | G protein-coupled receptor inhibitor and pharmaceutical product | |
| CN111793031A (zh) | 芳香胺类化合物及其在制备ar和brd4双重抑制剂和调控剂中的用途 | |
| US20160024083A1 (en) | Compounds and methods for treating cancers | |
| WO2022033380A1 (zh) | 一种mor受体激动剂化合物、制备方法及其用途 | |
| JP2010526845A (ja) | 低粘度アントラサイクリン製剤 | |
| CN101712707A (zh) | 罗红霉素三种晶型物质、制法以及药物组合物与用途 | |
| GB2263636A (en) | Substituted triazolinones, triazolinethiones, and triazolinimines as neurotensin antagonists | |
| GB2263635A (en) | Substitiuted triazoles as neurotensin antagonists | |
| RU2797622C2 (ru) | Модуляторы андрогенового рецептора и способы их применения | |
| CN103130853A (zh) | 罗红霉素晶c型物质、制法以及药物组合物与用途 | |
| WO2003050097A1 (en) | Sodium salt of benzyl thiazolidine-2,4-dione derivative and hydrate thereof | |
| CN1832725A (zh) | 含有三嗪的生物活性组合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070405 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070405 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20080605 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100629 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100928 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20101005 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20101029 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20101124 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110223 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110302 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110324 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20110426 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20110525 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140603 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 4754487 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |