DK2807187T3 - Peptidantagonister af calcitonin-cgrp-familien af peptidhormoner og deres anvendelse - Google Patents

Peptidantagonister af calcitonin-cgrp-familien af peptidhormoner og deres anvendelse Download PDF

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DK2807187T3
DK2807187T3 DK13703494.8T DK13703494T DK2807187T3 DK 2807187 T3 DK2807187 T3 DK 2807187T3 DK 13703494 T DK13703494 T DK 13703494T DK 2807187 T3 DK2807187 T3 DK 2807187T3
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Christopher J Soares
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Christopher J Soares
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    • 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
    • A61K38/225—Calcitonin gene related peptide
    • 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
    • A61K38/23—Calcitonins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • 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
    • A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
    • 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
    • A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
    • A61P5/22—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of calcitonin
    • 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
    • C07K14/57527—Calcitonin gene related peptide
    • 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
    • C07K14/585—Calcitonins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Organic Chemistry (AREA)
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Claims (10)

1. Calcitonin-gen-relateret peptidantagonist med strukturen med formel I: Xi-yi-Z1 (i), hvor X1 omfatter X^-X^-X^-X^-X^-X^-X17 (SEQ ID NO: 16), hvor X11 er valgt fra gruppen bestående af alanin (Ala), cystein (Cys), og glycin (Gly), og hvor X12 er valgt fra gruppen bestående af cystein (Cys) og serin (Ser), forudsat af en af X11 og X12 er Cys; X13 er valgt fra gruppen bestående af arginin (Arg), asparagin (Asn), asparaginsyre (Asp), og valin (Val); X14 er valgt fra gruppen bestående af leucin (Leu), phenylalanin (Phe), og threonin (Thr); X15 er valgt fra gruppen bestående af alanin (Ala), glycin (Gly), og serin (Ser); X16 er valgt fra gruppen bestående af alanin (Ala), isoleucin (Ile), leucin (Leu), og serin (Ser); X17 er Cys; og hvor Y1 er -Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-GIn-Thr-Tyr-Pro-Arg-Thr-Asn- (SEQ ID NO: 34); og Z1 er -Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 46).
2. Antagonist ifølge krav 1, hvor: X1 er valgt fra gruppen bestående af NH2-Ala-Cys-Asp-Thr-Ala-Ala-Cys-(SEQ ID NO: 17), NH2-Ala-Cys-Asp-Thr-Ala-Ser-Cys- (SEQ ID NO: 18), NH2-Ala-Cys-Asp-Thr-Ala-Val-Cys- (SEQ ID NO: 19), NH2-Ala-Cys-Asn-Thr-Ala-Ala-Cys- (SEQ ID NO: 20), NH2-Ala-Cys-Val-Leu-Gly-Ala-Cys- (SEQ ID NO:21), NH2-Ala-Cys-Arg-Phe-Gly-Ala-Cys- (SEQ ID NO: 22), NH2-Ala-Cys-Asp-Leu-Ser-Ala-Cys- (SEQ ID NO: 23), NH2-Ala-Cys-Asn-Leu-Ser-Ala-Cys-(SEQ ID NO: 24), Cys-Ser-Asn-Thr-Ala-Ala-Cys-(SEQ ID NO: 25), NH2-Ala-Cys-Asp-Thr-Ala-Leu-Cys- (SEQ ID NO: 26), NH2-Ala-Cys-Asp-Thr-Ala-Ile-Cys- (SEQ ID NO: 27), NH2-Ala-Cys-Asp-Leu-Ser-Val-Cys- (SEQ ID NO:
30), NH2-Ala-Cys-Asn-Leu-Ser-Val-Cys (SEQ ID NO: 32) og NH2-Cys-Ser-Asn-Thr-Ala-Val-Cys- (SEQ ID NO: 33); Y1 er -Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-GIn-Thr-Tyr-Pro-Arg-Thr-Asn- (SEQ ID NO: 34); og Z1 er -Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 46).
3. Antagonist ifølge krav 2 med strukturen: NH2-Ala-Cys-Asp-Thr-Ala-Ala-Cys-Val-Leu-Gly-Arg-Leu-Ser-Gln-Glu-Leu-His-Arg-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 1), NH2-Ala-Cys-Asp-Thr-Ala-Ser-Cys-Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-GIn-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 2), NH2-Ala-Cys-Asp-Thr-Ala-Val-Cys-Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-GIn-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 3), NH2-Ala-Cys-Asn-Thr-Ala-Ala-Cys-Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-GIn-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 4), NH2-Ala-Cys-Val-Leu-Gly-Ala-Cys-Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 5), NH2-Ala-Cys-Arg-Phe-Gly-Ala-Cys-Val-Leu-Gly-Arg-Leu-Ser-Gln-Glu-Leu-His-Arg-Leu-GIn-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 6), NH2-Ala-Cys-Asn-Leu-Ser-Ala-Cys-Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-GIn-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 7), NH2-Cys-Ser-Asn-Thr-Ala-Ala-Cys-Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-GIn-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 8), NH2-Ala-Cys- Asp-Thr-Ala-Leu-Cys-Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-l_ys-Ala-Phe-NH2 (SEQ ID NO: 9), NH2-Ala-Cys-Asp-Thr-Ala-Ile-Cys-Val-Leu-Gly-Arg-Leu-Ser-Gln-Glu-I_eu-His-Arg-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 10), Nhte-Ala-Cys-Asn-Leu-Ser-Val-Cys-Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-GIn-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 11), NH2-Cys-Ser-Asn-Thr-Ala-Val-Cys-Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-GIn-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2 (SEQ ID NO: 12), eller et farmaceutisk acceptabelt salt deraf.
4. Antagonist ifølge krav 1, omfattende aminosyresekvensen valgt fra gruppen bestående af SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, NH2-Ala-Cys-Asp-Leu-Ser-Ala-Cys-Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-GIn-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2 og Nhh-Ala-Cys-Asp-Leu-Ser-Val-Cys-Val-Leu-Gly-Arg-Leu-Ser-GIn-Glu-Leu-His-Arg-Leu-GIn-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH2.
5. Farmaceutisk sammensætning omfattende en farmaceutisk acceptabel excipiens og en calcitonin-gen-relateret peptidantagonist ifølge et hvilket som helst af kravene 1-4.
6. Farmaceutisk sammensætning ifølge krav 5 til anvendelse i behandlingen af hovedpine.
7. Farmaceutisk sammensætning ifølge krav 6 til anvendelse i behandlingen af migræne.
8. Calcitonin-gen-relateret peptidantagonist ifølge et hvilket som helst af kravene 1-4 til anvendelse i behandlingen af en tilstand associeret med anomale niveauer af CGRP.
9. Calcitonin-gen-relateret peptidantagonist ifølge krav 8 til anvendelse i behandlingen af hovedpine.
10. Calcitonin-gen-relateret peptidantagonist ifølge krav 9 til anvendelse i behandlingen af migræne.
DK13703494.8T 2012-01-26 2013-01-25 Peptidantagonister af calcitonin-cgrp-familien af peptidhormoner og deres anvendelse DK2807187T3 (da)

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