RU2012128547A - Дважды ацилированные производные glp-1 - Google Patents
Дважды ацилированные производные glp-1 Download PDFInfo
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- RU2012128547A RU2012128547A RU2012128547/10A RU2012128547A RU2012128547A RU 2012128547 A RU2012128547 A RU 2012128547A RU 2012128547/10 A RU2012128547/10 A RU 2012128547/10A RU 2012128547 A RU2012128547 A RU 2012128547A RU 2012128547 A RU2012128547 A RU 2012128547A
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- Prior art keywords
- compound
- derivative
- glp
- analogue
- diseases
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- 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 title claims abstract 5
- 102100025101 GATA-type zinc finger protein 1 Human genes 0.000 title claims abstract 3
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 title claims abstract 3
- 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 claims abstract 12
- 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 claims abstract 9
- 150000001413 amino acids Chemical class 0.000 claims abstract 8
- 238000012986 modification Methods 0.000 claims abstract 8
- 230000004048 modification Effects 0.000 claims abstract 8
- 102000009027 Albumins Human genes 0.000 claims abstract 6
- 108010088751 Albumins Proteins 0.000 claims abstract 6
- 150000001875 compounds Chemical class 0.000 claims abstract 6
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 claims abstract 4
- 229940125898 compound 5 Drugs 0.000 claims abstract 4
- 150000001408 amides Chemical class 0.000 claims abstract 3
- 150000002148 esters Chemical class 0.000 claims abstract 3
- 150000003839 salts Chemical class 0.000 claims abstract 3
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 claims abstract 2
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 claims abstract 2
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 claims abstract 2
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 claims abstract 2
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 claims abstract 2
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 claims abstract 2
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 claims abstract 2
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 claims abstract 2
- 229940125810 compound 20 Drugs 0.000 claims abstract 2
- 229940126086 compound 21 Drugs 0.000 claims abstract 2
- 229940125878 compound 36 Drugs 0.000 claims abstract 2
- 229940127573 compound 38 Drugs 0.000 claims abstract 2
- 229940125936 compound 42 Drugs 0.000 claims abstract 2
- 229940127271 compound 49 Drugs 0.000 claims abstract 2
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 claims abstract 2
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 claims abstract 2
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 claims abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 9
- 206010012601 diabetes mellitus Diseases 0.000 claims 6
- 201000010099 disease Diseases 0.000 claims 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims 3
- 208000002249 Diabetes Complications Diseases 0.000 claims 3
- 206010012655 Diabetic complications Diseases 0.000 claims 3
- 208000030814 Eating disease Diseases 0.000 claims 3
- 208000019454 Feeding and Eating disease Diseases 0.000 claims 3
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 3
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 claims 3
- 235000014632 disordered eating Nutrition 0.000 claims 3
- 230000037356 lipid metabolism Effects 0.000 claims 3
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 claims 1
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 claims 1
- MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 claims 1
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 claims 1
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 claims 1
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 claims 1
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 claims 1
- -1 Compound 55 Compound Chemical class 0.000 claims 1
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 claims 1
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 claims 1
- 229940127113 compound 57 Drugs 0.000 claims 1
- 229940125900 compound 59 Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- ZBELDPMWYXDLNY-UHFFFAOYSA-N methyl 9-(4-bromo-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate Chemical compound C12=C3SC(C(=N)OC)=NC3=CC=C2N=CN=C1NC1=CC=C(Br)C=C1F ZBELDPMWYXDLNY-UHFFFAOYSA-N 0.000 claims 1
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/605—Glucagons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/65—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
-
- 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
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
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- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
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- A—HUMAN NECESSITIES
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- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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Abstract
1. Производное аналога GLP-1, где аналог содержит первый остаток K в позиции, соответствующей позиции 37 GLP-1(7-37) (SEQ ID №1), второй остаток K в позиции, соответствующей позиции 26 GLP-1(7-37), где первый остаток K обозначен K, а второй остаток K обозначен K, а также не более десяти аминокислотных модификаций по сравнению с GLP-1(7-37), включая Kи Q или R в позиции, соответствующей позиции 34 в GLP-1(7-37),где производное содержит две альбумин-связывающие группировки, присоединенные к Kи K, соответственно, где альбумин-связывающая группировка включает пролонгирующую группировку формулы Соединение 2а:Соединение 2а:где y является целым числом в диапазоне 7-15;или его фармацевтически приемлемая соль, амид или сложный эфир.2. Производное по п.1, где аналог имеет не более пяти аминокислотных модификаций.3. Производное по п.1, где аналог содержит Impи/или Aib.4. Производное по п.1, где аналог содержит Aib.5. Производное по п.1, где аналог не содержит (Ни Q).6. Производное по п.1, где аналог содержит следующие аминокислотные модификации по сравнению с GLP-1(7-37) (SEQ ID №1): (8Aib, 34R, 37K).7. Производное по п.1, где аналог имеет только следующие аминокислотные модификации по сравнению с GLP-1(7-37) (SEQ ID №1): (8Aib, 34R, 37K).8. Производное по п.1, где y составляет 9.9. Производное по п.1, где альбумин-связывающая группировка также включает Соединение 6 и/или Соединение 5:Соединение 6:и/илиСоединение 5:где k является целым числом в диапазоне 1-5, и n является целым числом в диапазоне 1-5.10. Производное аналога GLP-1, выбранное среди следующих: Соединение 20, Соединение 21, Соединение 32, Соединение 34, Соединение 36, Соединение 38, Соединение 42, Соединение 47, Соединение 48, Соединение 49, Соединение 50, Соединение 52, Соединение 55, Со
Claims (14)
1. Производное аналога GLP-1, где аналог содержит первый остаток K в позиции, соответствующей позиции 37 GLP-1(7-37) (SEQ ID №1), второй остаток K в позиции, соответствующей позиции 26 GLP-1(7-37), где первый остаток K обозначен K37, а второй остаток K обозначен K26, а также не более десяти аминокислотных модификаций по сравнению с GLP-1(7-37), включая K37 и Q или R в позиции, соответствующей позиции 34 в GLP-1(7-37),
где производное содержит две альбумин-связывающие группировки, присоединенные к K26 и K37, соответственно, где альбумин-связывающая группировка включает пролонгирующую группировку формулы Соединение 2а:
Соединение 2а:
где y является целым числом в диапазоне 7-15;
или его фармацевтически приемлемая соль, амид или сложный эфир.
2. Производное по п.1, где аналог имеет не более пяти аминокислотных модификаций.
3. Производное по п.1, где аналог содержит Imp7 и/или Aib8.
4. Производное по п.1, где аналог содержит Aib8.
5. Производное по п.1, где аналог не содержит (Н31 и Q34).
6. Производное по п.1, где аналог содержит следующие аминокислотные модификации по сравнению с GLP-1(7-37) (SEQ ID №1): (8Aib, 34R, 37K).
7. Производное по п.1, где аналог имеет только следующие аминокислотные модификации по сравнению с GLP-1(7-37) (SEQ ID №1): (8Aib, 34R, 37K).
8. Производное по п.1, где y составляет 9.
10. Производное аналога GLP-1, выбранное среди следующих: Соединение 20, Соединение 21, Соединение 32, Соединение 34, Соединение 36, Соединение 38, Соединение 42, Соединение 47, Соединение 48, Соединение 49, Соединение 50, Соединение 52, Соединение 55, Соединение 56, Соединение 57, Соединение 58, Соединение 59, Соединение 60, Соединение 61, Соединение 62, Соединение 63, Соединение 65, Соединение 67 и Соединение 68; или его фармацевтически приемлемая соль, амид или сложный эфир.
11. Производное по любому из пп.1-10 для применения в качестве лекарственного средства.
12. Производное по любому из пп.1-10 для применения в лечении и/или профилактике всех форм сахарного диабета и связанных с ним заболеваний, таких как пищевые расстройства, сердечно-сосудистые заболевания, желудочно-кишечные заболевания, диабетические осложнения, критические заболевания и/или синдром поликистоза яичников; и/или для улучшения параметров липидного обмена, улучшения функционирования β-клеток и/или для отсрочки или предотвращения прогрессирования диабетического заболевания.
13. Применение производного по любому из пп.1-10 в производстве лекарственного средства для лечения и/или профилактики всех форм сахарного диабета и связанных с ним заболеваний, таких как пищевые расстройства, сердечно-сосудистые заболевания, желудочно-кишечные заболевания, диабетические осложнения, критические заболевания и/или синдром поликистоза яичников; и/или для улучшения параметров липидного обмена, улучшения функционирования β-клеток и/или для отсрочки или предотвращения прогрессирования диабетического заболевания.
14. Способ лечения и/или профилактики всех форм сахарного диабета и связанных с ним заболеваний, таких как пищевые расстройства, сердечнососудистые заболевания, желудочно-кишечные заболевания, диабетические осложнения, критические заболевания и/или синдром поликистоза яичников; и/или улучшения параметров липидного обмена, улучшения функционирования β-клеток и/или отсрочки или предотвращения прогрессирования диабетического заболевания путем введения фармацевтически активного количества производного по любому из пп.1-10.
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