EP1750528A2 - Dipeptidkonjugate als alpha-msh-antagonisten - Google Patents

Dipeptidkonjugate als alpha-msh-antagonisten

Info

Publication number
EP1750528A2
EP1750528A2 EP05770970A EP05770970A EP1750528A2 EP 1750528 A2 EP1750528 A2 EP 1750528A2 EP 05770970 A EP05770970 A EP 05770970A EP 05770970 A EP05770970 A EP 05770970A EP 1750528 A2 EP1750528 A2 EP 1750528A2
Authority
EP
European Patent Office
Prior art keywords
arg
palm
acid
group
pro
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.)
Withdrawn
Application number
EP05770970A
Other languages
English (en)
French (fr)
Inventor
Anne-Marie Pinel
Pascal Verdie
Pascaline Dubs
Jean Martinez
Gilles Subra
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Centre National de la Recherche Scientifique CNRS
Institut Europeen de Biologie Cellulaire
Universite de Montpellier
Original Assignee
Centre National de la Recherche Scientifique CNRS
Institut Europeen de Biologie Cellulaire
Universite de Montpellier
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from FR0405069A external-priority patent/FR2870242B1/fr
Application filed by Centre National de la Recherche Scientifique CNRS, Institut Europeen de Biologie Cellulaire, Universite de Montpellier filed Critical Centre National de la Recherche Scientifique CNRS
Priority to EP10157084A priority Critical patent/EP2228381A3/de
Publication of EP1750528A2 publication Critical patent/EP1750528A2/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0815—Tripeptides with the first amino acid being basic
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/18—Peptides; Protein hydrolysates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • 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
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06086—Dipeptides with the first amino acid being basic
    • C07K5/06095—Arg-amino acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/57—Compounds covalently linked to a(n inert) carrier molecule, e.g. conjugates, pro-fragrances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention relates to novel alpha-MSH antagonist dipeptide conjugates and their use as a medicament or as a depigmentant.
  • the melanocortin receptors belong to the superfamily of seven transmembrane receptors coupled to the G protein and they stimulate the cAMP signal transduction pathway (Cône et al. Recent Prog. Horm. Res. 1996, 51, pages 287 -317).
  • the melanocortin system is involved in multiple physiological pathways including pigmentation, inflammation, erectile function, eating behavior, energy homeostasis, weight homeostasis and the function of the exocrine glands.
  • the ligands of the endogenous agonists for these melanocortin receptors are derived by post-translational modification of the transcript of the proopiomelanocortin gene, which during differential treatment leads to the generation of the hormones ⁇ , ⁇ and stimulating melanocytes (MSH) and of the corticotrophin (ACTH).
  • the melanocortin receptor subtypes are activated by all endogenous melanocortin peptides, with the exception of the melanocortin MC 2 receptor which is only stimulated by corticotrophin.
  • the melanocortin receptor family also has two endogenous antagonists, agouti and agouti related protein (AGRP) (Lu et al.
  • this compound is of high molecular weight and therefore has very limited therapeutic or cosmetic activity. Indeed, its size makes it difficult to optimize and its bioavailability is limited. In addition, it is expensive and difficult to prepare.
  • the tripeptide D-Trp-Arg-Leu-NH 2 (Proc. Natl. Acad. Sci. (1995), 92, pages 2894 - 2898) also has antagonistic activity. However, it contains tryptophan which is an unstable amino acid and can therefore cause storage stability problems.
  • EP 1 174 437 describes di or tripeptides comprising a naphthyl group and in particular a naphthylalanyl group. However, the presence of the naphthyl group increases the manufacturing price of the product. Furthermore, in certain countries such as Japan, peptides based on non-natural amino acids cannot be sold for cosmetic applications. In addition, no dipeptide activity is indicated.
  • dipeptides conjugated at the C-terminal with carboxylic acids have an alpha MSH antagonist activity. These antagonists have a very low molecular weight, are therefore easy to optimize, have good bioavailability and are very easy to prepare.
  • the present invention therefore relates to a dipeptide conjugate of general formula I below: A-AA2 -AA1 -NH 2 I in which A represents the radical corresponding to a monocarboxylic acid of general formula II below: HOOC-R II in which R represents
  • AA1 and AA2 represent identical or different amino acids chosen from the group formed by Ala, Asn, Cys, Gin, Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val, Asp, Glu, Arg, His, Lys, Orn, Dap, Dab, les corresponding amino homo acids and corresponding beta amino acids, in the form of enantiomers or diastereoisomers and their mixtures, including racemic mixtures.
  • the amino acids in the dipeptide conjugate of formula (I) can have a D, L or DL configuration if not otherwise specified.
  • the dipeptide conjugates of formula (I) can contain one or more asymmetric carbon atoms. They can therefore exist in the form of enantiomers or diastereoisomers. These enantiomers, diastereoisomers, as well as their mixtures, including racemic mixtures are part of the invention.
  • Gly Gly, Glycine, - Ile, 1 Isoleucine, - Leu, Leucine, - Met, Methionine, - Phe, Phenylalanine, or its analogs, in particular a halogen derivative, in particular para-fluoro-Phe, Homo-Phe, para-nitro-Phe or phenylglycine, - Pro, Proline, - Ser, Serine, - Thr, Th eonine, Trp, Tryptophan, - Tyr, Tyrosine, - Val, Valine, - Asp, Aspartic Acid, - Glu, Glutamic Acid,
  • dipeptide conjugates mentioned above and forming the subject of the present invention are obtained in the terminal NH 2 form (in other words having an amide function).
  • the conjugated dipeptides according to the present invention are linked in the form of salts or esters to the acid of formula II.
  • the conjugations according to this invention can be carried out by reacting the acid function of the amino acid with the acid function of the acid of formula II, or even it is possible to take advantage of the presence of a hydroxy function on the acid of formula II .
  • the present invention relates to all of these conjugations as well as the non-functional conjugates.
  • the conjugations are physical or chemical.
  • At least one of the amino acids AA2 or AA1, advantageously both, represents a basic amino acid, advantageously chosen from the group consisting of Arg, His, Dap, Dab, Orn or Lys, advantageously it is Arg.
  • Advantageously AA2 represents a basic amino acid advantageously chosen from the group consisting of Arg, His, Lys, Orn, Dap or Dab, advantageously it is Arg.
  • Advantageously AA1 and / or AA2 do not represent Trp.
  • Advantageously AA1 and / or AA2 do not represent Cys.
  • at least one of the amino acids AA1 or AA2 is chosen from the group consisting of Ser and Pro.
  • Advantageously AA1 represents Pro.
  • Advantageously AA2 represents Ser.
  • the acid of formula (II) is a polyunsaturated fatty acid, that is to say comprising from 1 to 6 unsaturations. Even more advantageously, it is an omega-3 acid.
  • these omega-3 acids there may be mentioned in particular ⁇ -linolenic acid, cervonic acid, timnodonic acid and pinolenic acid.
  • Acids cervonic, timnodonic and pinolenic are also known by the respective names of 4, 7, 10, 13, 16, 19-docosahexaenoic acid (DHA), 5, 8, 11, 14, 17-eicosapentaenoic acid (EPA) and 5,9,12- octodecatrienoic acid.
  • A represents a monocarboxylic acid radical of general formula (II), it can advantageously be chosen from acetic acid, myristic acid, palmitic acid, hydroxydecenoic and decenoic acids and in particular, trans- 10-hydroxy- ⁇ 2-decenoic and trans-oxo-9-decene-2-oic acid.
  • the acid of formula (II) is an acid chosen from lipoic acid (Lip) or its reduced form dihydrolipoic acid, N-lipoyl-lysine or phenylbutyric acid (Pbu).
  • Lip lipoic acid
  • Pbu phenylbutyric acid
  • A represents the radical corresponding to palmitic acid (Palm).
  • dipeptide conjugates of the invention mention may be made of the dipeptide conjugates chosen from the group consisting of a) A-Arg-His-NH 2 , b) A-Arg-Arg-NH 2 , c) A-Arg-Pro- NH 2 . d) A-Arg-Lys-NH 2 , e) A-Ser-Pro-NH 2 . f) A-DPhe-Arg-NH 2 . in which A has the definition given above.
  • dipeptide conjugates of the invention mention may be made of the dipeptide conjugates chosen from the group consisting of 39) Palm-Arg-His-NH 2 , 41) Palm-Arg-Arg-NH 2 , 49) Palm-Arg-Pro- NH 2 , 50) Palm-Arg-Lys-NH 2 , 125) Palm-Ser-Pro-NH 2 . 269) Palm-DPhe-Arg-NH 2 , 362) Pbu-DPhe-Arg-NH 2 , 363) Lip-DPhe-Arg-NH 2 .
  • the dipeptide conjugates which are the subject of the present invention can be obtained either advantageously by conventional chemical synthesis, or by enzymatic synthesis, according to any methods known to those skilled in the art.
  • the present invention further relates to a cosmetic, dermatological or pharmaceutical composition or a food supplement comprising a dipeptide conjugate according to the present invention and optionally a cosmetically or pharmaceutically acceptable excipient.
  • the dipeptide conjugates can be administered for cosmetic or pharmaceutical use topically. They can also be used in food supplements, in other words in the oral nutraceutical field.
  • the dipeptide conjugates according to the invention are preferably administered, topically.
  • compositions according to the present invention intended for topical administration may be in the forms which are usually known for this type of administration, that is to say in particular lotions, foams, gels, dispersions, sprays, serums, masks, body milks, ointments, solutions, emulsions, gels, or creams for example, with excipients allowing in particular skin penetration to improve the properties and accessibility of the active ingredient.
  • compositions generally contain, in addition to the dipeptide conjugate according to the present invention, a physiologically acceptable medium, generally based on water or on a solvent, for example alcohols, ethers or glycols.
  • They can also contain surfactants, preservatives, stabilizing agents, emulsifiers, thickeners, other active ingredients leading to a complementary or possibly synergistic effect, trace elements, essential oils, perfumes, dyes, collagen, chemical or mineral filters, moisturizers or thermal waters.
  • the dipeptide conjugate according to the invention can be present at a concentration between 10 "8 M and 10 " 3M, advantageously between 10 "7 M and 10 " 5 M.
  • the present invention further relates to a dipeptide conjugate according to the present invention or a pharmaceutical composition according to the present invention for its use as a medicament, advantageously intended to prevent, improve or treat immune abnormalities, immunodeficiency, regulate body weight by controlling appetite, treating disorders of the central nervous system, regulating satiety, treating anorexia or certain skin cancers.
  • the present invention further relates to the use of a cosmetic composition according to the present invention as a depigmenting agent, for lightening or whitening the epidermis, eliminating spots on the skin, in particular of old age or freckle, or preventing pigmentation. of the epidermis.
  • the present invention relates to a cosmetic treatment method for lightening, depigmenting or whitening the epidermis, eliminating spots on the skin, in particular of old age or freckles, or preventing pigmentation of the epidermis, comprising application to the skin of a cosmetic composition according to the present invention.
  • a 361-member acylated dipeptide library was synthesized using SynPhase TM Lanterns and a "split and pool” color marking strategy as described in the article by Feliu et al. (J. Comb. Chem., 2003, 5, pages 256-361).
  • the chemicals used are the following: Amino acids protected at the N-terminus by an ⁇ -Fmoc group, Fmoc-Ala-OH, Fmoc-D-Ala-OH, Fmoc- Arg (Pbf) -OH, Fmoc -D-Arg (Pbf) -OH, Fmoc-His (Trt) -OH, Fmoc-D-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Phe-OH, Fmoc-D-Phe -OH, Fmoc-Trp (Boc) -OH, Fmoc-D-Trp (Boc) -OH, Fmoc-Met-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc- Leu -OH, Fmoc-Tyr (
  • the coupling agent HBTU (2- (1-H-benzotriazol-1-yl) -1, 1, 3, 3-tetramethyl-uronium hexafluorophosphate) was purchased from SENN chemicals.
  • N N-dimethylformamide (DMF), dichloromethane, methanol, acetonitrile, ethyl ether, trifluoroacetic acid (TFA), piperidine were purchased from Riedel-de Ha ⁇ n, Carlo Erba or Acros organics and used without purification.
  • N, N-diisopropylethylamine (DIEA), triisopropylsilane, palmitic acid were purchased from Aldrich or Avocado. All reagents and chemicals were of analytical grade and were used without further purification.
  • the Rink amide Synphase Polystyrene Lanterns of the D series were supplied by Mi otopes, Pty.
  • the standard process for manufacturing these dipeptides includes the following steps: 1- Standard Fmoc deprotection protocol
  • the Fmoc deprotection steps were carried out by immersing the lanterns immobilized on a support of 96 stems in a mixture of dimethylsulfoxide (DMF) / piperidine (80/20, v / v) for 30 minutes. Rectangular polypropylene containers the same size as a standard 96-well plate were used. The excess deprotection solution was simply removed by vigorously shaking the support of the rods.
  • DMF dimethylsulfoxide
  • piperidine 80/20, v / v
  • washing steps were carried out by successively immersing the lanterns arranged in a Multipin format in polypropylene containers containing DMF (3 x 5 min), methanol (2 x 5 min) and dichloromethane (DCM) (1 x 5 min), successively.
  • the lanterns were air dried for 5 min in a steam hood after the last washing with DCM.
  • 3- Standard coupling protocol 0.4 M solutions of each amino acid Fmoc, HBTU and DIEA were prepared in DMF and kept at 4 ° C. throughout the synthesis. 200 ⁇ l of amino acid solution were distributed in 96-well deep plates. 200 ⁇ l of DIEA solution and 200 ⁇ l of HBTU solution were added then and finally, the support of the rods carrying the lanterns was adapted to the deep well plate for 2 hours.
  • HPLC analyzes were performed on a Waters Alliance 2690 HPLC system and a Waters 996 photodiode array detector and a C18 Merck Chromolith Speed ROD column of 50 x 4.6 mm. A flow rate of 5 ml / min and a gradient from 100% B to 100% C over 3 min were used (Eluent B, water / 0.1% TFA; Eluent C, acetonitrile / 0.1% TFA ). The purity estimates are based on the percentage area of the peaks detected at 214 nm.
  • the LC / SM system consisted of a Waters Alliance 2690 HPLC coupled to a Micromass Platform II spectrometer (ionization by electrospray mode, ESI +). All analyzes were performed using a Waters Symmetry C18 column, 3.5 ⁇ m, 2.1 x 30 mm. A flow rate of 600 ⁇ l / min and a gradient from 100% B to 100% C over 3 min were used (Eluent B, water / 0.1% TFA; Eluent C, acetonitrile / 0.1% TFA ).
  • the mass spectra by positive ion electrospray were acquired at a solvent flow rate of 100 ml / min. Nitrogen was used for both the nebulizing gas and the drying gas. The data was acquired in read mode from / z 400 to 1400 in 0.1 ⁇ 3 intervals; 10 readings were added to produce the final spectrum.
  • Palm Leu Lys NH 2 100 496.4 146 Palm Leu Asn NH 2 15 482.4 147 Palm Leu Met NH 2 100 499.3 148 Palm Leu DPhe NH 2 100 515.4 149 Palm Leu DTrp NH 2 87 554.4 150 Palm Leu DArg NH 2 100 524.4 151 Palm Leu DHisNH 2 86 505.4 152 Palm Leu DAlaNH 2 100 439.3
  • Palm- dipeptides according to the present invention were added at various concentrations and each The measurement was made in triplicate and two or three series of experiments were carried out.
  • the cells were maintained in modified Eagle medium from Dulbecco with 10% fetal calf serum (FCS), 1 mM glutamine, 100 U / ml of penicillin and 10 "4 g / ml of streptomycin.
  • FCS fetal calf serum
  • the cells were maintained at 37 ° C in a 5% CO 2 atmosphere and the cell culture media were renewed every two days.
  • the cells were plated on a 96-well plate (Nunc, Roskilde) 24 hours before contact with the dipeptides according to the invention.
  • the cAMP was measured as follows: The cells plated the day before at 8.10 4 cells per well are placed in the presence of one of the 5 dipeptide conjugates according to the invention at various concentrations for 10 minutes at 37 ° C. with 5.10 " 8M of ⁇ -MSH. After this time, the lysis of the cells was carried out and the cAMP content was measured using a competitive binding test kit (RPN225, Amersham Pharmacia Biotech). Each independent experiment was carried out at least twice in triplicate.
  • the peptide activity was determined by referring to the level of cAMP synthesized by untreated cells and to the production of cAMP induced by -MSH alone. The curves were adjusted and the IC 50 values were determined with nonlinear regression in the GraphPad Prism (GraphPad software, San Diego, CA, United States). The results are presented in the following Table 2.
  • the Palm-dipeptides tested appeared to be antagonists of the human MC X melanocortin receptor using lines M4Be melanoma cells. These dipeptide conjugates have an IC 50 in a micromolar range. These dipeptides are the first example of short synthetic antagonist compounds binding to the MCi receptor and they open up the field of non-peptide small molecule antagonists of ⁇ -MSH. In particular, these compounds comprise an arginine residue in position AA2. Interestingly, compound 125 (Palm-Ser-Pro-NH 2 ), having no basic residue in its sequence, showed an IC 50 value of 17 ⁇ M. This result has shown that the binding to the MC X receptor does not necessarily require a positively charged radical. With only two amino acid residues, these palmitoyl compounds can be considered as useful lead compounds for the design of non-peptide ⁇ -MSH antagonists.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Dermatology (AREA)
  • Immunology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Birds (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Child & Adolescent Psychology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Psychiatry (AREA)
  • Toxicology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Cosmetics (AREA)
EP05770970A 2004-05-11 2005-05-10 Dipeptidkonjugate als alpha-msh-antagonisten Withdrawn EP1750528A2 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP10157084A EP2228381A3 (de) 2004-05-11 2005-05-10 Konjugierte Dipeptid-ALPHA-MSH-Antagonisten-Komplexe

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR0405069A FR2870242B1 (fr) 2004-05-11 2004-05-11 Peptides ou conjugues peptidiques derives de la msh et leur utilisation dans le traitement cosmetique de la canitie.
FR0411279A FR2870244B1 (fr) 2004-05-11 2004-10-22 Conjugues dipeptidiques antagonistes de l'alpha-msh
PCT/FR2005/001164 WO2005115174A2 (fr) 2004-05-11 2005-05-10 Conjugues dipeptidiques antagonistes de l’alpha-msh

Publications (1)

Publication Number Publication Date
EP1750528A2 true EP1750528A2 (de) 2007-02-14

Family

ID=34973223

Family Applications (2)

Application Number Title Priority Date Filing Date
EP10157084A Withdrawn EP2228381A3 (de) 2004-05-11 2005-05-10 Konjugierte Dipeptid-ALPHA-MSH-Antagonisten-Komplexe
EP05770970A Withdrawn EP1750528A2 (de) 2004-05-11 2005-05-10 Dipeptidkonjugate als alpha-msh-antagonisten

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP10157084A Withdrawn EP2228381A3 (de) 2004-05-11 2005-05-10 Konjugierte Dipeptid-ALPHA-MSH-Antagonisten-Komplexe

Country Status (6)

Country Link
US (1) US8097590B2 (de)
EP (2) EP2228381A3 (de)
JP (2) JP4897969B2 (de)
CA (1) CA2566478A1 (de)
FR (3) FR2870244B1 (de)
WO (1) WO2005115174A2 (de)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2870244B1 (fr) * 2004-05-11 2011-01-07 Centre Nat Rech Scient Conjugues dipeptidiques antagonistes de l'alpha-msh
DE102006011883A1 (de) * 2006-03-09 2007-09-13 Beiersdorf Ag Tropolon- und Hydroxybenzol-substituierte Oligopeptide zur Depigmentierung
FR2900573B1 (fr) * 2006-05-05 2014-05-16 Sederma Sa Nouvelles compositions cosmetiques renfermant au moins un peptide contenant au moins un cycle aromatique bloque
CN107028792A (zh) * 2008-05-29 2017-08-11 唐纳德·欧文 皮肤美容组合物中的寡聚生物表面活性剂
CA2853791C (en) * 2011-10-28 2017-10-24 Ruey J. Yu N-acyldipeptide derivatives and their uses
DK2827907T3 (da) * 2012-03-20 2019-06-11 Helix Biomedix Inc Korte antimikrobielle lipopeptider
FR2998570B1 (fr) 2012-11-26 2016-12-02 Sederma Sa Peptides, compositions les comprenant et utilisations notamment cosmetiques propigmentantes
KR101553637B1 (ko) * 2014-01-27 2015-09-16 (주)셀인바이오 펩타이드 지방산 유도체 및 이를 함유하는 주름 개선용 화장품 조성물
EP3393604B1 (de) 2015-12-24 2026-02-11 Unilever Global IP Limited Tyrosinasehemmer
FR3047990B1 (fr) * 2016-02-18 2020-12-25 Rpm Dermatologie Composition cosmetique cutanee comprenant un peptide sdkp ou un analogue de celui-ci
US12435056B2 (en) 2016-03-14 2025-10-07 Neostrata Company, Inc. N-lipoic-amino acid or peptide, derivatives and their uses
EP3429577B1 (de) * 2016-03-14 2021-12-29 NeoStrata Company, Inc. N-lipon-aminosäure oder peptide, derivate und deren verwendungen
WO2019208700A1 (ja) * 2018-04-26 2019-10-31 ゼリア新薬工業株式会社 ジペプチド及びこれを含有する医薬組成物
CN111100890B (zh) * 2018-10-26 2022-04-08 中国石油化工股份有限公司 一种提高木质纤维素糖化率的方法
KR102163568B1 (ko) * 2020-08-21 2020-10-07 주식회사 비드테크 지방산 항균펩타이드 및 이를 함유하는 항균 조성물
CN114292312B (zh) * 2022-01-13 2025-10-14 湖南微肽生物医药有限公司 一种全液相合成9肽-1的方法

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1184770C2 (de) 1961-06-01 1965-09-02 Hoffmann La Roche Verfahren zur Herstellung von antibacteriell wirksamen Peptiden
FR1327363A (fr) * 1962-05-21 1963-05-17 Hoffmann La Roche Peptides et procédé pour leur préparation
US5674839A (en) 1987-05-22 1997-10-07 Competitive Technologies, Inc. Cyclic analogs of alpha-MSH fragments
EP0389950A1 (de) 1989-03-23 1990-10-03 Lion Corporation Inhibitor des melanocytenstimulierenden Hormons und dieses enthaltendes, äusserlich anwendbares Präparat
AU5609694A (en) * 1992-11-24 1994-06-22 University Of Cincinnati, The Melanogenic inhibitor, and methods of producing and using the same
FR2710340B1 (fr) 1993-09-22 1995-12-15 D Hinterland Lucien Dussourd Dérivés peptidiques de l'alpha-MSH et leur application .
US5786332A (en) * 1995-03-06 1998-07-28 Trega Biosciences, Inc. Cytokine restraining agents and methods of use in pathologies and conditions associated with altered cytokine levels
US6054556A (en) * 1995-04-10 2000-04-25 The Arizona Board Of Regents On Behalf Of The University Of Arizona Melanocortin receptor antagonists and agonists
JP4105763B2 (ja) * 1995-06-23 2008-06-25 ザ ガバメント オブ ザ ユナイテッド ステイツ オブ アメリカ，アズ リプレゼンテッド バイ ザ セクレタリー デパートメント オブ ヘルス アンド ヒューマン サービシーズ アグーチシグナルタンパク質およびそのペプチドの脱色活性
FR2741075B1 (fr) * 1995-11-15 1998-01-30 Rech De Pathologie Appliquee S Conjugues peptidiques, leur utilisation a titre de medicament et compositions les contenant
US5714567A (en) * 1996-02-15 1998-02-03 Council Of Scientific & Ind. Research Process for the preparation of aromatic polyesters
US6372717B1 (en) * 1996-08-23 2002-04-16 Sederma S.A. Synthetic peptides and their use in cosmetic or dermopharmaceutical compositions
DE19653736C2 (de) 1996-12-12 2002-11-21 Lancaster Group Gmbh Kosmetisches Präparat mit Peptidzusatz
US6228840B1 (en) * 1998-02-27 2001-05-08 Edward T. Wei Melanocortin receptor antagonists and modulations of melanocortin receptor activity
FR2781157B1 (fr) 1998-07-15 2000-08-25 Oreal Composition anti-inflammatoire
WO2000064926A1 (fr) * 1999-04-26 2000-11-02 Ajinomoto Co., Inc. Inhibiteur hormonal stimulant les melanocytes
FR2805744B1 (fr) 2000-03-03 2006-08-25 Sederma Sa Compositions cosmetiques ou dermopharmaceutiques contenant le dipeptide val-trp pour faciliter le drainage lymphatique et diminuer la masse adipeuse
BR0111718A (pt) 2000-06-16 2003-09-09 Hercules Inc Peptìdeos quimicamente modificados, composições e métodos de produção e uso
FR2810323B1 (fr) 2000-06-16 2002-09-06 Shiseido Int France Utilisation cosmetique d'un lipopeptide
US6911447B2 (en) 2001-04-25 2005-06-28 The Procter & Gamble Company Melanocortin receptor ligands
US20030194445A1 (en) * 2001-11-12 2003-10-16 Kuhner Carla H. Compositions and methods of use of peptides in combination with biocides and/or germicides
JP4158382B2 (ja) * 2002-01-30 2008-10-01 株式会社ナリス化粧品 口紅用組成物
FR2835528B1 (fr) * 2002-02-01 2004-03-12 Inst Europ Biolog Cellulaire Nouveaux derives peptidiques, leur preparation et leur application therapeutique et cosmetique
FR2836042B1 (fr) * 2002-02-15 2004-04-02 Sederma Sa Compositions cosmetiques ou dermopharmaceutiques pour diminuer les poches et cernes sous les yeux
US20040010010A1 (en) * 2002-04-30 2004-01-15 Ebetino Frank Hallock Melanocortin receptor ligands
US7034004B2 (en) 2002-05-07 2006-04-25 University Of Florida Peptides and methods for the control of obesity
PL1625150T3 (pl) 2003-05-08 2007-05-31 Dsm Ip Assets Bv Tripeptydy i ich pochodne do stosowania w kosmetyce w celu poprawy struktury skóry
WO2004110341A2 (en) 2003-06-19 2004-12-23 Yeda Research & Development Co. Ltd. Antimicrobial and anticancer lipopeptides
FR2870244B1 (fr) * 2004-05-11 2011-01-07 Centre Nat Rech Scient Conjugues dipeptidiques antagonistes de l'alpha-msh
FR2870242B1 (fr) 2004-05-11 2010-08-20 Inst Europeen Biologie Cellulaire Peptides ou conjugues peptidiques derives de la msh et leur utilisation dans le traitement cosmetique de la canitie.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2005115174A2 *

Also Published As

Publication number Publication date
JP4897969B2 (ja) 2012-03-14
US8097590B2 (en) 2012-01-17
CA2566478A1 (fr) 2005-12-08
FR2945809A1 (fr) 2010-11-26
FR2941459A1 (fr) 2010-07-30
WO2005115174A2 (fr) 2005-12-08
WO2005115174A3 (fr) 2006-05-26
US20070231284A1 (en) 2007-10-04
EP2228381A2 (de) 2010-09-15
JP2010235608A (ja) 2010-10-21
FR2870244B1 (fr) 2011-01-07
JP2007537213A (ja) 2007-12-20
FR2870244A1 (fr) 2005-11-18
EP2228381A3 (de) 2010-12-29

Similar Documents

Publication Publication Date Title
FR2941459A1 (fr) Conjugues dipeptidiques antagonistes de l'alpha-msh
WO2000043417A1 (fr) Utilisation cosmetique ou pharmaceutique de peptides pour la regulation des dysfonctionnements immunologiques et dans l'inflammation cutanes
US11357783B2 (en) Conjugate of finasteride with peptide
FR2835528A1 (fr) Nouveaux derives peptidiques, leur preparation et leur application therapeutique et cosmetique
CA2566481C (fr) Peptides ou conjugues peptidiques derives de la msh et leur utilisation dans le traitement cosmetique de la canitie
EP1745071B1 (de) Tripeptidkonjugate als msh-agonisten
EP0316322B1 (de) Tetrapeptid-hemmstoff zum eintritt in den kreislauf von hemopoietischen stammzellen, verfahren zu deren herstellung und deren anwendungen
EP0837881A2 (de) KONJUGATE VON alpha-MSH MIT EINER FETTSÄURE, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG ALS MEDIKAMENT
CN110612125B (zh) 异维a酸和肽的偶联物
CA2532869C (fr) Nouveaux conjugues peptidiques utiles dans le traitement preventif et curatif de l`alopecie
OA19680A (en) Conjugate of Isotretinoin and Peptide.
EA041637B1 (ru) Конъюгат изотретиноина с пептидом

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20061208

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR

DAX Request for extension of the european patent (deleted)
RIN1 Information on inventor provided before grant (corrected)

Inventor name: VERDIE, PASCAL

Inventor name: SUBRA, GILLES

Inventor name: PINEL, ANNE-MARIE

Inventor name: DUBS, PASCALINE

Inventor name: MARTINEZ, JEAN

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS

Owner name: INSTITUT EUROPEEN DE BIOLOGIE CELLULAIRE

Owner name: UNIVERSITE DE MONTPELLIER I

Owner name: UNIVERSITE MONTPELLIER 2 SCIENCES ET TECHNIQUES

17Q First examination report despatched

Effective date: 20100729

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20130219