DE602004004156T2 - 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 - Google Patents
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 Download PDFInfo
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- DE602004004156T2 DE602004004156T2 DE602004004156T DE602004004156T DE602004004156T2 DE 602004004156 T2 DE602004004156 T2 DE 602004004156T2 DE 602004004156 T DE602004004156 T DE 602004004156T DE 602004004156 T DE602004004156 T DE 602004004156T DE 602004004156 T2 DE602004004156 T2 DE 602004004156T2
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- 239000000203 mixture Substances 0.000 title claims abstract description 235
- 150000001875 compounds Chemical class 0.000 title claims abstract description 90
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 22
- 239000000556 agonist Substances 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 title abstract description 33
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- 108010088406 Glucagon-Like Peptides Proteins 0.000 title 2
- -1 GLP-1 compound Chemical class 0.000 claims abstract description 43
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims abstract description 11
- 102100025101 GATA-type zinc finger protein 1 Human genes 0.000 claims abstract 3
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- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 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
- 238000000605 extraction Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000003269 fluorescent indicator Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 229960005051 fluostigmine Drugs 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
- 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
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 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
- 230000002473 insulinotropic effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- UTUVQTIFVPMOCQ-UHFFFAOYSA-N methyl 2-(benzenecarbonothioylsulfanyl)acetate Chemical compound COC(=O)CSC(=S)C1=CC=CC=C1 UTUVQTIFVPMOCQ-UHFFFAOYSA-N 0.000 description 1
- YBKDJCVIHWOEEW-UHFFFAOYSA-N methyl 3-[4-(2-aminophenyl)-1,3-oxazol-2-yl]propanoate Chemical compound O1C(CCC(=O)OC)=NC(C=2C(=CC=CC=2)N)=C1 YBKDJCVIHWOEEW-UHFFFAOYSA-N 0.000 description 1
- VBVMAZHWZFPGPT-UHFFFAOYSA-N methyl 3-[4-(2-nitrophenyl)-1,3-oxazol-2-yl]propanoate Chemical compound O1C(CCC(=O)OC)=NC(C=2C(=CC=CC=2)[N+]([O-])=O)=C1 VBVMAZHWZFPGPT-UHFFFAOYSA-N 0.000 description 1
- JGTDEHLLRKQPDL-UHFFFAOYSA-N methyl 4-[4-(2-aminophenyl)-1,3-oxazol-2-yl]butanoate Chemical compound O1C(CCCC(=O)OC)=NC(C=2C(=CC=CC=2)N)=C1 JGTDEHLLRKQPDL-UHFFFAOYSA-N 0.000 description 1
- HURZMSZDVGMYKJ-UHFFFAOYSA-N methyl 4-amino-4-oxobutanoate Chemical compound COC(=O)CCC(N)=O HURZMSZDVGMYKJ-UHFFFAOYSA-N 0.000 description 1
- SRXOJMOGPYFZKC-UHFFFAOYSA-N methyl 4-chloro-4-oxobutanoate Chemical compound COC(=O)CCC(Cl)=O SRXOJMOGPYFZKC-UHFFFAOYSA-N 0.000 description 1
- FYJDBTBFSPFPIU-UHFFFAOYSA-N methyl 5-[2-(2-methoxyphenyl)-1,3-oxazol-5-yl]pentanoate Chemical compound O1C(CCCCC(=O)OC)=CN=C1C1=CC=CC=C1OC FYJDBTBFSPFPIU-UHFFFAOYSA-N 0.000 description 1
- WXTVYFSMVXSQCQ-UHFFFAOYSA-N methyl 5-[2-(2-methoxyphenyl)-1,3-thiazol-4-yl]pentanoate Chemical compound COC(=O)CCCCC1=CSC(C=2C(=CC=CC=2)OC)=N1 WXTVYFSMVXSQCQ-UHFFFAOYSA-N 0.000 description 1
- OVTNQEONMLTACH-UHFFFAOYSA-N methyl 5-[4-(2-aminophenyl)-1,3-oxazol-2-yl]pentanoate Chemical compound O1C(CCCCC(=O)OC)=NC(C=2C(=CC=CC=2)N)=C1 OVTNQEONMLTACH-UHFFFAOYSA-N 0.000 description 1
- CDOKZYRBEFSWPK-UHFFFAOYSA-N methyl 5-[4-(2-methoxyphenyl)-5-methyl-1,3-oxazol-2-yl]pentanoate Chemical compound O1C(CCCCC(=O)OC)=NC(C=2C(=CC=CC=2)OC)=C1C CDOKZYRBEFSWPK-UHFFFAOYSA-N 0.000 description 1
- FBYOUVUZIMHBEH-UHFFFAOYSA-N methyl 5-[4-[2-(methanesulfonamido)phenyl]-1,3-oxazol-2-yl]pentanoate Chemical compound O1C(CCCCC(=O)OC)=NC(C=2C(=CC=CC=2)NS(C)(=O)=O)=C1 FBYOUVUZIMHBEH-UHFFFAOYSA-N 0.000 description 1
- FTDKKFRBIPXYRN-UHFFFAOYSA-N methyl 5-[5-(2-hydroxyphenyl)-1,2,4-oxadiazol-3-yl]pentanoate Chemical compound COC(=O)CCCCC1=NOC(C=2C(=CC=CC=2)O)=N1 FTDKKFRBIPXYRN-UHFFFAOYSA-N 0.000 description 1
- VKXHACKQVLLDMB-UHFFFAOYSA-N methyl 5-[5-(2-methoxyphenyl)-1,3-oxazol-2-yl]pentanoate Chemical compound O1C(CCCCC(=O)OC)=NC=C1C1=CC=CC=C1OC VKXHACKQVLLDMB-UHFFFAOYSA-N 0.000 description 1
- MNOHXVBSGSQEPX-UHFFFAOYSA-N methyl 5-[5-(2-methoxyphenyl)triazol-1-yl]pentanoate Chemical compound COC(=O)CCCCN1N=NC=C1C1=CC=CC=C1OC MNOHXVBSGSQEPX-UHFFFAOYSA-N 0.000 description 1
- OQEZMRVNSROGPF-UHFFFAOYSA-N methyl 5-azidopentanoate Chemical compound COC(=O)CCCCN=[N+]=[N-] OQEZMRVNSROGPF-UHFFFAOYSA-N 0.000 description 1
- YKFKZLYDQJHAQB-UHFFFAOYSA-N methyl 5-nitropentanoate Chemical compound COC(=O)CCCC[N+]([O-])=O YKFKZLYDQJHAQB-UHFFFAOYSA-N 0.000 description 1
- ANPQFIMPPYLNRE-UHFFFAOYSA-N methyl 8-[(2-hydroxy-2-phenylethyl)amino]-8-oxooctanoate Chemical compound COC(=O)CCCCCCC(=O)NCC(O)C1=CC=CC=C1 ANPQFIMPPYLNRE-UHFFFAOYSA-N 0.000 description 1
- HAUKRIWANMCVAG-UHFFFAOYSA-N methyl 8-[4-(2-propan-2-yloxyphenyl)imidazol-1-yl]octanoate Chemical compound COC(=O)CCCCCCCN1C=NC(C=2C(=CC=CC=2)OC(C)C)=C1 HAUKRIWANMCVAG-UHFFFAOYSA-N 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- ALWDVDJEMWKXEY-UHFFFAOYSA-N n'-methylbutanediamide Chemical compound CNC(=O)CCC(N)=O ALWDVDJEMWKXEY-UHFFFAOYSA-N 0.000 description 1
- CBQNSTKQBGIAEL-UHFFFAOYSA-N n-[(2-methoxyphenyl)methylidene]hydroxylamine Chemical compound COC1=CC=CC=C1C=NO CBQNSTKQBGIAEL-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 1
- 238000012585 nuclear overhauser effect spectroscopy experiment Methods 0.000 description 1
- 229940078552 o-xylene Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000001301 oxygen Substances 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
- 230000000144 pharmacologic effect Effects 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 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
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-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
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 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
- 230000008569 process Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-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
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- KKKDGYXNGYJJRX-UHFFFAOYSA-M silver nitrite Chemical compound [Ag+].[O-]N=O KKKDGYXNGYJJRX-UHFFFAOYSA-M 0.000 description 1
- KZJPVUDYAMEDRM-UHFFFAOYSA-M silver;2,2,2-trifluoroacetate Chemical compound [Ag+].[O-]C(=O)C(F)(F)F KZJPVUDYAMEDRM-UHFFFAOYSA-M 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 1
- 229910001488 sodium perchlorate Inorganic materials 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical class [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- XCAQIUOFDMREBA-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(=O)OC(C)(C)C XCAQIUOFDMREBA-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 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
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical class [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- 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
- C07D263/34—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/48—Nitrogen atoms not forming part of a nitro radical
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicinal Preparation (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49653703P | 2003-08-20 | 2003-08-20 | |
| US496537P | 2003-08-20 | ||
| PCT/US2004/024386 WO2005019184A1 (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 (2)
| Publication Number | Publication Date |
|---|---|
| DE602004004156D1 DE602004004156D1 (de) | 2007-02-15 |
| DE602004004156T2 true DE602004004156T2 (de) | 2007-10-11 |
Family
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Family Applications (1)
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|---|---|---|---|
| DE602004004156T Expired - Lifetime DE602004004156T2 (de) | 2003-08-20 | 2004-08-18 | 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 |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US7662771B2 (enExample) |
| EP (1) | EP1658273B1 (enExample) |
| JP (1) | JP4767850B2 (enExample) |
| AT (1) | ATE350369T1 (enExample) |
| CA (1) | CA2532026C (enExample) |
| DE (1) | DE602004004156T2 (enExample) |
| ES (1) | ES2278346T3 (enExample) |
| WO (1) | WO2005019184A1 (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2286679T3 (es) * | 2003-08-20 | 2007-12-01 | Eli Lilly And Company | Compuestos, procedimientos y formulaciones para la liberacion oral de un compuesto de peptido de tipo glucagon (glp)-1 o un peptido agonist a del receptor de melanocortina 4 (mc4). |
| EP1658273B1 (en) * | 2003-08-20 | 2007-01-03 | Eli Lilly And Company | Compounds, methods and formulations for the oral delivery of a glucagon like peptide (glp)-1 compound or an melanocortin 4 receptor (mc4) agonist peptide |
| EP1915168A4 (en) | 2005-07-08 | 2010-03-31 | Ipsen Pharma | LIGANDS OF MELANOCORTIN RECEPTORS |
| ES2663916T3 (es) | 2005-07-08 | 2018-04-17 | Ipsen Pharma | Ligandos de los receptores de la melanocortina |
| CA2618628C (en) | 2005-08-18 | 2014-11-18 | Synta Pharmaceuticals Corp. | Triazole compounds that modulate hsp90 activity |
| EP2057112B1 (en) | 2006-08-31 | 2018-12-19 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| NZ579403A (en) * | 2007-02-08 | 2012-03-30 | Synta Pharmaceuticals Corp | Triazole compounds that are useful in the treatment of proliferative disorders, such as cancer |
| JP2011518841A (ja) | 2008-04-24 | 2011-06-30 | ニューリンク ジェネティクス, インコーポレイテッド | Ido阻害剤 |
| WO2009139181A1 (ja) | 2008-05-15 | 2009-11-19 | 大正製薬株式会社 | 4員環構造を有する10a-アザライド化合物 |
| WO2011045418A1 (en) * | 2009-10-16 | 2011-04-21 | Dsm Ip Assets B.V. | Azido alkanoic acids and derivatives thereof in feed for reducing methane formation emanating from the digestive activities of ruminants |
| JP6588027B2 (ja) | 2014-10-24 | 2019-10-09 | 武田薬品工業株式会社 | 複素環化合物 |
| MX385777B (es) | 2014-12-24 | 2025-03-04 | Lg Chemical Ltd | Derivado de biarilo como agonista de gpr120. |
| WO2016168388A2 (en) | 2015-04-14 | 2016-10-20 | Palatin Technologies, Inc. | Therapies for obesity, diabetes and related indications |
| CN107163011B (zh) * | 2017-05-27 | 2019-10-01 | 上海应用技术大学 | 3-(3,4,5-三甲氧基苯甲酰)-苯并呋喃类微管蛋白抑制剂及其制备方法和用途 |
| CN113248455A (zh) * | 2021-05-25 | 2021-08-13 | 湖北科技学院 | 一种3,5-二取代异噁唑类衍生物及其合成方法 |
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| EP1658273B1 (en) * | 2003-08-20 | 2007-01-03 | Eli Lilly And Company | Compounds, methods and formulations for the oral delivery of a glucagon like peptide (glp)-1 compound or an melanocortin 4 receptor (mc4) agonist peptide |
-
2004
- 2004-08-18 EP EP04779446A patent/EP1658273B1/en not_active Expired - Lifetime
- 2004-08-18 DE DE602004004156T patent/DE602004004156T2/de not_active Expired - Lifetime
- 2004-08-18 JP JP2006523865A patent/JP4767850B2/ja not_active Expired - Fee Related
- 2004-08-18 WO PCT/US2004/024386 patent/WO2005019184A1/en not_active Ceased
- 2004-08-18 ES ES04779446T patent/ES2278346T3/es not_active Expired - Lifetime
- 2004-08-18 CA CA2532026A patent/CA2532026C/en not_active Expired - Fee Related
- 2004-08-18 US US10/566,342 patent/US7662771B2/en not_active Expired - Lifetime
- 2004-08-18 AT AT04779446T patent/ATE350369T1/de not_active IP Right Cessation
-
2009
- 2009-12-11 US US12/636,244 patent/US8552039B2/en not_active Expired - Fee Related
-
2013
- 2013-08-20 US US13/971,680 patent/US8765796B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ES2278346T3 (es) | 2007-08-01 |
| ATE350369T1 (de) | 2007-01-15 |
| JP4767850B2 (ja) | 2011-09-07 |
| US20100120876A1 (en) | 2010-05-13 |
| WO2005019184A1 (en) | 2005-03-03 |
| CA2532026A1 (en) | 2005-03-03 |
| US8765796B2 (en) | 2014-07-01 |
| US20080214448A1 (en) | 2008-09-04 |
| EP1658273B1 (en) | 2007-01-03 |
| US8552039B2 (en) | 2013-10-08 |
| DE602004004156D1 (de) | 2007-02-15 |
| EP1658273A1 (en) | 2006-05-24 |
| US7662771B2 (en) | 2010-02-16 |
| CA2532026C (en) | 2012-04-17 |
| US20140031287A1 (en) | 2014-01-30 |
| JP2007502816A (ja) | 2007-02-15 |
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Owner name: EMISPHERE TECHNOLOGIES, INC., TARRYTOWN, N.Y., US |
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Representative=s name: KROHER, STROBEL RECHTS- UND PATENTANWAELTE, 80336 |
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