DK3157949T3 - Exendin-4-derivater som selektive glucagonreceptor-agonister - Google Patents

Exendin-4-derivater som selektive glucagonreceptor-agonister Download PDF

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DK3157949T3
DK3157949T3 DK15731876.7T DK15731876T DK3157949T3 DK 3157949 T3 DK3157949 T3 DK 3157949T3 DK 15731876 T DK15731876 T DK 15731876T DK 3157949 T3 DK3157949 T3 DK 3157949T3
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amino acid
acid residue
leu
ser
residue selected
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DK15731876.7T
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Torsten Haack
Siegfried Stengelin
Andreas Evers
Michael Wagner
Bernd Henkel
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Sanofi Sa
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    • 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
    • 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
    • A61K38/2278—Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • 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
    • C07K14/57563—Vasoactive intestinal peptide [VIP]; Related peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Claims (23)

1. Peptidforbindelse med formel (I): Tza-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-X10-Ser-Lys-Gln-X14-Glu-Ser-Arg- Arg-Ala-Gln-X21-Phe-lle-Glu-Trp-Leu-Leu-Ala-X29-Gly-Pro-Glu-Ser-Gly-Ala- Pro-Pro-Pro-Ser-R1 (i) hvor X10 er en aminosyrerest valgt blandt Tyr, Leu, Val, Ile, Phe, phenylglycin, 1-naphthylalanin, 2-fluorphenylalanin, cyclohexylglycin og tert-leucin, X14 er en aminosyrerest valgt blandt Leu og Nle X21 er en aminosyrerest valgt blandt Asp og Glu, X29 er en aminosyrerest valgt blandt Gly og Thr, R1 er OH eller NH2, eller et salt eller solvat deraf.
2. Forbindelse ifølge krav 1, hvor den C-terminale gruppe R1 er OH.
3. Forbindelse ifølge et hvilket som helst af kravene 1 til 2, hvor X10 er Leu, X14 er en aminosyrerest valgt blandt Leu og Nle X21 er en aminosyrerest valgt blandt Asp og Glu, X29 er en aminosyrerest valgt blandt Gly og Thr, R1 er OH, eller et salt eller solvat deraf.
4. Forbindelse ifølge et hvilket som helst af kravene 1 til 2, hvor X10 er Tyr, X14 er en aminosyrerest valgt blandt Leu og Nle, X21 er Glu, X29 er en aminosyrerest valgt blandt Gly og Thr, R1 er OH, eller et salt eller solvat deraf.
5. Forbindelse ifølge et hvilket som helst af kravene 1 til 2, hvor X10 er 1-naphthylalanin, X14 er en aminosyrerest valgt blandt Leu og Nle, X21 er en aminosyrerest valgt blandt Asp og Glu, X29 er Thr, R1 er OH, eller et salt eller solvat deraf.
6. Forbindelse ifølge et hvilket som helst af kravene 1 til 2, hvor X10 er cyclohexylglycin, X14 er en aminosyrerest valgt blandt Leu og Nle, X21 er en aminosyrerest valgt blandt Asp og Glu, X29 er Thr, R1 er OH, eller et salt eller solvat deraf.
7. Forbindelse ifølge et hvilket som helst af kravene 1 til 2, hvor X10 er en aminosyrerest valgt blandt Tyr, Leu, Val, Ile, phenylglycin, 1-naphthylalanin, 2-fluorphenylalanin og cyclohexylglycin, X14 er Leu, X21 er en aminosyrerest valgt blandt Asp og Glu, X29 er en aminosyrerest valgt blandt Gly og Thr, R1 er OH, eller et salt eller solvat deraf.
8. Forbindelse ifølge et hvilket som helst af kravene 1 til 2, hvor X10 er en aminosyrerest valgt blandt Tyr, Leu, Ile, Phe, 1-naphthylalanin, cyclohexylglycin og tert-leucin, X14 er Nle, X21 er en aminosyrerest valgt blandt Asp og Glu, X29 er Thr, R1 er OH, eller et salt eller solvat deraf.
9. Forbindelse ifølge et hvilket som helst af kravene 1 til 2, hvor X10 er en aminosyrerest valgt blandt Leu, Phe, 1-naphthylalanin, 2-fluorphenylalanin og cyclohexylglycin, X14 er en aminosyrerest valgt blandt Leu og Nle X21 er Asp, X29 er Thr, R1 er OH, eller et salt eller solvat deraf.
10. Forbindelse ifølge et hvilket som helst af kravene 1 til 2, hvor X10 er en aminosyrerest valgt blandt Tyr, Leu, Val, Ile, phenylglycin, 1-naphthylalanin, cyclohexylglycin og tert-leucin, X14 er en aminosyrerest valgt blandt Leu og Nle, X21 er Glu, X29 er en aminosyrerest valgt blandt Gly og Thr, R1 er OH, eller et salt eller solvat deraf.
11. Forbindelse ifølge et hvilket som helst af kravene 1 til 2, hvor X10 er en aminosyrerest valgt blandt Tyr, Leu, Val, Ile, Phe, phenylglycin, 1-naphthylalanin, 2-fluorphenylalanin, cyclohexylglycin og tert-leucin, X14 er en aminosyrerest valgt blandt Leu og Nle, X21 er en aminosyrerest valgt blandt Asp og Glu, X29 er Thr, R1 er OH, eller et salt eller solvat deraf.
12. Forbindelse ifølge et hvilket som helst af kravene 1 til 2, hvor X10 er en aminosyrerest valgt blandt Tyr, Leu og Val, X14 er Leu, X21 er Glu, X29 er Gly, R1 er OH, eller et salt eller solvat deraf.
13. Forbindelse ifølge et hvilket som helst af kravene 1 til 12 valgt blandt forbindelserne med SEQ ID NO: 3 til 25 samt salte eller solvater deraf.
14. Forbindelse ifølge et hvilket som helst af kravene 1 til 13 valgt blandt forbindelserne med SEQ ID NO: 3, 5, 6, 9, 15, 20, 23, 24 og 25 samt salte eller solvater deraf.
15. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse i medicin, især i human medicin.
16. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse ifølge krav 15, der er til stede som et aktivt middel i en farmaceutisk sammensætning sammen med mindst ét farmaceutisk acceptabelt bæremateriale.
17. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse ifølge krav 15 eller 16 sammen med mindst ét yderligere terapeutisk aktivt middel, hvor det yderligere terapeutisk aktive middel er valgt fra gruppen, der består af insulin og insulinderivater valgt blandt Glargin/Lantus®, Glulisin/Apidra®, Detemir/Levemir®, Lispro/Humalog®/Liprolog®, Degludec/DegludecPlus, Aspart, basalinsulin, LY2963016, PEGylated insulin Lispro (LY2605541), Humulin®, SuliXen®, NN1045, Insulin plus Symlin®, hurtigt virkende og korttidsvirkende insuliner valgt blandt Linjeta™, PH20, NN1218 og HinsBet®, (APC-002) hydrogel, orale, inhalerbare, transdermale og sublinguale insuliner valgt blandt Exubera®, Nasulin®, Afrezza®, Tregopil, TPM 02, Capsulin™, Oral-lyn®, Cobalamin® oral insulin, ORMD-0801, NN1953 og VIAtab™ og HM12460A (LAPS insulin), GLP-1, GLP-l-analoger og GLP-l-receptoragonister valgt blandt Lixisenatid/AVEO 010/ZP10/Lyxumia®, Exenatid/Exendin- 4/Byetta®/Bydureon®/ITCA 650, Liraglutid/Victoza®, Semaglutid, Taspoglutid, Albiglutid, Dulaglutid, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, HM-112600, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, MAR-701, ZP-2929, ZP-3022, CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatid-XTEN og Glucagon-XTEN, MAR709, HM1525A, tripel GLP1-receptor/glucagonreceptor/GIP-receptor-agonister, kombinationer af GLPl-receptoragonister med insulinderivater valgt blandt IDegLira og Lixilan, dobbelte GLP1/glucagonreceptoragonister, dobbelte GLP1/GIP-receptoragonister, glucagonreceptoragonister og GIP-receptoragonister eller -antagonister.
18. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse til behandling af hypoglykæmi, forhøjede niveauer af blodglucose eller til anvendelse til supplerende behandling med insulin.
19. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse til reducering og opretholdelse af kropsvægten, som antidot til forgiftning med beta-blokkere og calciumkanalblokkere og til inducering af midlertidig relaksation af mave-tarm-systemet til radiologiske anvendelser.
20. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse til behandling eller forebyggelse af hypoglykæmi, type 2-diabetes mellitus og til anvendelse til forsinkelse af progression fra prædiabetes til type 2-diabetes.
21. Farmaceutisk sammensætning, der omfatter mindst én forbindelse ifølge et hvilket som helst af kravene 1 til 14 eller et fysiologisk acceptabelt salt eller solvat af en hvilken som helst af disse.
22. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse i en fremgangsmåde til behandling af hypoglykæmi, hvor en effektiv mængde af mindst én forbindelse med formel I ifølge et hvilket som helst af kravene 1 til 14 er til administration med en effektiv mængde af mindst én anden forbindelse, der er anvendelig til behandling af hypoglykæmi, og hvor administrationen især er samtidig administration, separat administration eller sekventiel administration.
23. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse ifølge krav 22, hvor administrationen er parenteral administration.
DK15731876.7T 2014-06-18 2015-06-17 Exendin-4-derivater som selektive glucagonreceptor-agonister DK3157949T3 (da)

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EP14305935 2014-06-18
PCT/EP2015/063607 WO2015193381A1 (en) 2014-06-18 2015-06-17 Exendin-4 derivatives as selective glucagon receptor agonists

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US (1) US9932381B2 (da)
EP (1) EP3157949B1 (da)
JP (1) JP6581606B2 (da)
KR (1) KR20170018433A (da)
CN (1) CN106715466B (da)
AR (1) AR100888A1 (da)
AU (1) AU2015276203B2 (da)
BR (1) BR112016029582A2 (da)
CA (1) CA2951077A1 (da)
CY (1) CY1121032T1 (da)
DK (1) DK3157949T3 (da)
ES (1) ES2691534T3 (da)
HR (1) HRP20181708T1 (da)
HU (1) HUE039702T2 (da)
IL (1) IL249583A0 (da)
LT (1) LT3157949T (da)
MX (1) MX367348B (da)
PL (1) PL3157949T3 (da)
PT (1) PT3157949T (da)
RU (1) RU2017101377A (da)
SG (1) SG11201609478PA (da)
SI (1) SI3157949T1 (da)
TR (1) TR201815158T4 (da)
TW (1) TW201613633A (da)
UY (1) UY36179A (da)
WO (1) WO2015193381A1 (da)

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