WO2008020778A1 - Famille de peptides dotés d'une activité analgésique - Google Patents
Famille de peptides dotés d'une activité analgésique Download PDFInfo
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- WO2008020778A1 WO2008020778A1 PCT/RU2006/000404 RU2006000404W WO2008020778A1 WO 2008020778 A1 WO2008020778 A1 WO 2008020778A1 RU 2006000404 W RU2006000404 W RU 2006000404W WO 2008020778 A1 WO2008020778 A1 WO 2008020778A1
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- dldhpro
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- 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
- C07K5/10—Tetrapeptides
- C07K5/1021—Tetrapeptides with the first amino acid being acidic
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides 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
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- 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
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/101—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- 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
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1013—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
-
- 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
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1016—Tetrapeptides 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
- C07K5/10—Tetrapeptides
- C07K5/1019—Tetrapeptides with the first amino acid being basic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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 the use of peptides of the general formula A-B-Tyr-Pro (DPro, dHPro, DdHPro, DLdHPro, Hyp) -B-X below as analgesic analgesics.
- narcotic morphine and structures close to it
- non-narcotic analgesics derivatives of salicylic acid, pyrazolone, aniline, etc.
- Endogenous ligands of peptide nature responsible for the physiological analgesic effects of enkephalins and endorphins, are known in mammals.
- another class of endogenous peptides - dinorphins, in particular dermorphin [Emelyanova T.G.,
- the cited amino acid sequences possessing analgesic activity have a common pattern, namely, the presence of the Tyr-Pro peptide sequence (DPro, dHPro, DdHPro, DLdHPro, Nur) in the 1,2 or 2,3 positions of the above peptides in the structure.
- DPro, dHPro, DdHPro, DLdHPro, Nur the Tyr-Pro peptide sequence
- A-B-Tyr-Pro (DPro, d ⁇ r GmbH, Dd ⁇ r consumer, DLd ⁇ r technically, Hyp) -BX (I), where A is O, -AIa, -Asp, -GIu, -Phe, -GIy, -His, -Pe, -Lus, -Leu, -Met, -Pro, -Arg, -Ser, -Thr,
- X is OH, -OCH 3 , -NH 2 .
- the invention relates to the field of physiology and pharmacology for the creation of new drugs and may find application in medicine.
- the technical result achieved by the present invention is the creation of new peptides that meet the general formula (I), the identification of their useful analgesic properties and the directed development of medicinal products based on them preparations.
- the specified technical result is achieved in that it allows the directional synthesis of various peptide sequences corresponding to the general formula (I) according to the general scheme.
- Tyr-Gly-Tyr-DLd ⁇ r Williams- ⁇ modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier modifier- ⁇
- Tyr-Ala-Tyr-DLd ⁇ r Albany-Gl dilemma Tyr-Ala-Tyr-DLdHPro-Gly-NH 2 ⁇ ur-Ala-Tur-DLd ⁇ r-Gl dilemma- ⁇
- Tur-Ala-Tur-DLd ⁇ r Geneva-Ala-Tur-DLd ⁇ r
- Tur-Ala-Tur-DLd ⁇ r Geneva-Ala-Tur-DLd ⁇ r
- Ala-Glu-Tur-DLdHPro-GI involves Ala-Gly-Tyr-DLdHPro-Gly-NH 2 Ala-Glu-Tur-DLdHrro-GIu-OCH
- Ser-Il Pain-Tur-DLd ⁇ r
- Ser-Il Springfield-Tur-DLd ⁇ r
- Val-Val-Tur-DLdHPro-Ala Val-VaI-Tyr-DLdHPro-Ala-NH 2 ⁇ a-Va-Tur-DLdHPro-Ala-OCH
- Val-Val-Tur-DLdHPro-Glu Val-Val-Tyr-DLdHPro-Glu-NH 2 v ⁇ al-Val-Tur-DLdHPro-Glu-OCH
- Val-Val-Tur-DLd ⁇ r Ltd., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Inc., Japan, Vapentad ⁇ , Vapentad, Vapentad, Inc., Vap-Val-Tur-DLd ⁇ r, Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc
- Val-Val-Tur-DLd ⁇ r Williams-Lus Val-Val-Tyr-DLdHPro-Lys-NH 2 Val-Val-Tur-DLd ⁇ rro-Lus-OCH
- Val-Val-Tur-DLd ⁇ r Desired Val-Val-Tur-DLd ⁇ r
- Val-Val-Tur-DLd ⁇ r Desired Val-Val-Tur-DLd ⁇ r
- Val-Val-Tur-DLd ⁇ r Desired Val-Val-Tur-DLd ⁇ r
- Val-Val-Tur-DLd ⁇ r Desired Val-Val-Tur-DLd ⁇ r
- Val-Val-Tyr-DLd ⁇ r Summary- ⁇ Val-Val-Tyr-DLdHPro-Trp- ⁇ 2 Val-Val-Tur-DLd ⁇ r- ⁇ modifier
- Val-Val-Tur-DLdHPro-Tur Val-Val-Tyr-DLdHPro-Tyr-NH 2 Val-Val-Tur-DLdHr-Tur-OCH
- Lus-Arg-Tur-DLdHPro-Il Korean Lys-Arg-Tyr-DLdHPro-1 Ie-NH 2 Lus-Arg-Tur-DLdHPro-I Ie-OCH 3
- Tur-Il-Tur-DLd ⁇ r Albany-Asr Tur-Il
- Tur-Il-Tur-DLd ⁇ r Albany-Asr Tur-Il
- Tur-Il Springfield-Tur-DLd ⁇ r-ASp-NH 2
- Tur-Il Springfield-Tur-DLd ⁇
- Tur-Ilé-Tug-DLd ⁇ r 6- ⁇
- Tur-Il-Tur-DLd ⁇ Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc., Inc.,
- Tur-Il-Tur-DLd ⁇ r Albany-Il-Tur-DLd ⁇ r
- Ser-Asr-Tug-DLd ⁇ r must-II
- Ser-Asr-Tur-DLd ⁇ r must-Il
- Ser-Asr-Tur-DLd ⁇ r Although- ⁇ opposition attend Ser-Asr-Tur-DLd ⁇ r?-Tur-N H 2 Ser-Asr-Tur-DLd ⁇ r arise-Tur- ⁇
- Pro-Va ⁇ -Tur-DLdHPro-GI involves Pro-VaI-Tyr-DLdHPro-Gly-NH 2 ⁇ ro-Val-Tur-DLdHPro-Glu-OCH
- Tyr-Leu-Tyr-DLd ⁇ r Albany-Leu-Tyr-DLd ⁇ r
- Tyr-Leu-Tyr-DLd ⁇ r desires to be kept in the middle position.
- Tyr-Leu-Tyr-DLd ⁇ r desires to be kept in the middle position.
- Tyr-Leu-Tyr-DLd ⁇ r Williams- ⁇ is Tyr-Leu-Tyr-DLdHPro-His-NH 2 ⁇ ur-Leu-Tur-DLd ⁇ r- ⁇ is- ⁇
- Tyr-Leu-Tyr-DLd ⁇ r Although-Leu-Tyr-DLd ⁇ r, Ltd- ⁇ modifier modifier Tyr-Leu-Tyr-DLdHPro-Trp-NH 2 ⁇ ur-Leu-Tur-DLd ⁇ rschreib- ⁇ modifier modifier- ⁇
- Val-Pro-Tyr-DLdHPro-Asp Val-Pro-Tyr-DLdHPro-Asp-NH 2 Val-Pro-Tyr-DLdHPro-Asp-OCH 3
- Val-Pro-Tur-DLdHPro-Glu Val-Pro-Tyr-DLdHPro-G! Y-NH 2 Val-Pro-Tur-DLdHr-Glu-OCH
- Val-Pro-Tur-DLdHPro-Tur Val-Pro-Tyr-DLdHPro-Tyr-NH 2 Val-Pro-Tur-DLdHr-Tur-OCH
- Val-GIu-Tur-DLdHPro-Ala VaI-Gly-Tyr-DLdHPro-AIa-NH 2
- Val-Glu-Tur-DLdHPro-Asr Val-Gly-Tyr-DLdHPro-Asp- ⁇ H 2 Va-Glu-Tur-DLdHPro-Asr-OCH
- Val-Glu-Tur-DLdHPro-Phe Val-Gly-Tyr-DLdHPro-Phe-NH 2 Val-Glu-Tur-DLdHPro-Phe-OCH
- Val-GIu-Tur-DLdHPro-His Val-Gly-Tyr-DLdHPro-His-NH 2 Val-Gly-Tyr-DLdHPro-His-OCH 3
- Val-Glu-Tur-DLdHPro-Ser Val-Gly-Tyr-DLdHPro-Ser- 2 Val-Glu-Tur-DLdHr-Ser-OCH
- Val-Glu-Tur-DLdHPro-Ala Val-Glu-Tyr-DLdHPro-AIa-NH 2 Val-Glu-Tur-DLdHPro-A Ia-OCH 3
- Val-Glu-Tur-DLdHPro-Asr Val-Glu-Tyr-DLdHPgo-Asp-NH 2 Va-Glu-Tur-DLdHPro-Asr-OCH
- Val-Glu-Tyr-DLdHPro-Phe Val-Glu-Tyr-DLdHPro-Phe-NH 2 Val-Glu-Tur-DLdHpro-Phe-OCH
- Val-Glu-Tur-DLdHPro-His Val-Glu-Tyr-DLdHPro-His-NH 2 Val-Glu-Tur-DLdHPro-His-OCH
- Val-Glu-Tur-DLdHPro-Pe Val-Glu-Tyr-DLdHPro-Ile-NH 2 Val-Glu-Tyr-DLdHPro-Ile-OCH 3
- Val-Glu-Tur-DLdHPro-Met VaI-Glu-Tyr-DLdHPro-Met-NH 2 Val-GIu-Tur-DLdHr-Met-OCH
- Val-Glu-Tur-DLdHPro-Arg Val-Glu-Tyr-DLdHPro-Arg-NH 2 Val-Glu-Tur-DLdHrr-Arg-OCH
- Val-Glu-Tur-DLdHPro-Trr Val-Glu-Tyr-DLdHPro-Trp-NH 2 Val-Glu-Tuh-DLdHrr-Trr-OCH
- Val-Glu-Tur-DLdHPro-Tur Val-Glu-Tyr-DLdHPro-Tyr-NH 2 Val-Glu-Tur-DLdHr-Tur-OCH
- Met-Met-Tur-DLd ⁇ r Tol, Met-Met-Tur-DLd ⁇ r must-I Ie Met-Met-Tyr-DLdHPro- ⁇ e-NH 2 Met-Met-Tur-DLd ⁇ r must-Il flesh- ⁇
- Met-Met-Tur-DLd ⁇ r erie-Met-Tur-DLd ⁇ r
- Met-Met-Tur-DLd ⁇ r erie-Met-Tur-DLd ⁇ r
- Met-Met- ⁇ ur-DLd ⁇ r erie-Met-Tur-DLd ⁇ r
- Met-Met-Tur-DLdHPro-Met Met-Met-Tyr-DLdHPro-Met-NH 2 Met-Met-Tur-DLdHPro-Met-OCH Met-Met-Tur-DLd ⁇ r Ltd- ⁇ convinced Met-Met-Tyr-DLdHPro-Pro-NH 2 ⁇ et-Met-Tur-DLd ⁇ r
- Met-Met-Tur-DLd ⁇ r Korean-V Corporation's Met-Met-Tur-DLd ⁇ r-VaI-NH 2 Met-Met-Tur-DLd ⁇ r-VaI-OCH 3
- Met-Il-Tur-DLd ⁇ r Albany-Glu Met-IIe-Tyr-DLdHPro-Glu-NH 2 ⁇ et-Il Skin-Tur-DLd ⁇ modifierr-Glu- ⁇
- Met-Il To-Tur-DLd ⁇ r
- et-II To-Tur-DLd ⁇ modifierr
- Met-Il To-Tur-DLd ⁇ r
- Met-Ile-Tyr-DLdHPro-Gly-NH 2 Att- ⁇ , wishes-Tur-DLd ⁇ r
- Met-Il To-Tur-DLd ⁇ r
- Met- ⁇ To-Tur-DLd ⁇ r
- Met- ⁇ To-Tyr-DLdHPro-Lys-NH 2 ⁇
- Statt-I To-Tur-DLd ⁇ r
- Met-Il-Tur-DLd ⁇ r desires-Met Met-II Canal-Tur-DLd ⁇ r and-Met-N ⁇ Met- ⁇ mecanic-Tyr-DLdHPro-Met-OCH 3
- Met-Il To-Tur-DLd ⁇ r
- To-Tur-DLd ⁇ r To-Tur-DLd ⁇ r
- Ala-Ser-Tur-DLdHPro-Il Korean Ala-Ser-Tyr-DLdHPro-IIe-NH 2 Ala-Ser-Tur-DLdHPro-IIe-OCH-,
- Ala-Ala-Tur-DLdHPro-Asr Ala-AIa-Tyr-DLdHPro-Asp-NH 2 Ala-Ala-Tur-DLdHPro-Asr-OCH
- the peptides of formula (I) were synthesized by peptide chemistry, both in solution and by solid-phase synthesis using L and D amino acids, as well as L, D and DL dehydro-amino acids (3,4-dehydro-amino acid in formula (I) , in the tables and examples given is indicated by dHPrutton).
- Table 2 shows the peptides of formula (I) synthesized by peptide chemistry in solution.
- the synthesis of the tripeptide HCl-H-Tyg-3,4-DLdHPro-Ser-OCH3 was carried out by condensation of the dipeptide DiBoc-Tyr-3,4-DLdHPro and HCl-H-Seg-OCH 3 using peptide chemistry in solution. Fragments were synthesized using tetrabutylammonium salts (TBA) and the activated ester method. Evaporation of the solutions was carried out on a vacuum evaporator at 40 ° C.
- TSA tetrabutylammonium salts
- DiBoc-Tyr-3,4-DLdHPgo 1.32 g (2.76 mmol) was dissolved in 20 ml of acetonitrile, an excess of (1,3) N-hydroxysuccinimide 412.8 mg (3.59 mmol) was added, cooled to 0 ° C and an excess of (1.3) DCCH was added 810.88 mg (3.59 mmol).
- DCCH was added 810.88 mg (3.59 mmol).
- HPLC Results Zorbach Column SB-AQ Cl 8, 4.6 x 150 mm; flow rate 1 ml / min; eluent 5% MeOH - 50 mM buff, pH 2.8), linear gradient, temperature 30 ° C, pressure 9.0 MPa, exit time 7.73 min.
- Example 2 Table 3 shows examples of the synthesis of peptides by the automatic solid-phase method.
- the peptides shown in Table 3 were synthesized by the automatic solid-phase method according to the Fmoc scheme on the Rink polymer (4- (2,4-dimethoxyphenyl-fluorenylmethoxy-aminomethyl) phenoxypolyistol, 0.5 mmol of amino groups per 1 g of the polymer) using the HEPTDI method. Peptides were cleaved from the polymer and released with a mixture of TFA: m-crezole (95: 5).
- the peptides were purified using reverse phase HPLC (Juriteg Cis column (10x250 mm) in the following acetonitrile gradient: 5 min at 2%, then a linear gradient from 2 to 60% in 50 min in 0.1% trifluoroacetate buffer at a flow rate of 4 ml / min Peptides were characterized using mass spectrometry (MALDI).
- MALDI mass spectrometry
- Tail-off test - tilil flisk (D'Amor, 1941). The animal was placed in an individual plastic chamber, the tail was immersed 5 cm in a vessel with water with a temperature of 55 ⁇ 1 ° C. The tail jerk reflex closes at the level of the spinal cord.
- the latent period of getting rid of the pain stimulus was recorded - the time period (sec) during which the animal pulled its tail out of the water completely. The maximum time for presentation of a pain stimulus is 30 seconds.
- the initial pain sensitivity was determined as the arithmetic mean of the indicators recorded at 60, 40, and 20 minutes before injection. The latent period of getting rid of the pain stimulus was fixed 20, 40, and 60 120 minutes after administration.
- Analgesic activity was evaluated by changing the latent period of the reaction according to the formula: where LP 0P - latent period of disposal after the introduction of the substance, LP IC ⁇ - the arithmetic mean of the latent periods of disposal before the introduction of the substance.
- Tyr-Pro-Ser-NH 2 a significant extension of the reaction time for 90 minutes after injection.
- Tur-Pro-Ser-OCH3 and Tyr-Pro-Lys-NH 2 caused an analgesic effect for one hour.
- Effect DLdNRro-Tyr-Ser-OCH, Tyr-dHPro-Ser-NH 2 was developed 40 min after administration and lasted for up to 60 minutes at DLdNRro-Tyr-Ser-OCH and up to 90 minutes at Tur- dHPro-Ser-NH 2.
- Tyr-DPro-Ser-OCH 3 caused an analgesic reaction at 20 and 40 minutes after administration.
- Glu-Tyr-DPro-Ser-NH 2 possessed the greatest analgesic activity. An increase in the latent period of the reaction was observed within 90 minutes of observation.
- Tyr-Pro-GIy-Pm-NH 2 and Tyr-Tyr-Pro-Ser-NH 2 lengthened the latent period of tail withdrawal during the 60 minutes of observation.
- the effect of Ala-Tur-DPro-Seg-NH and DAla-Tur-DPro-Ser-NH began at 40 minutes after administration and lasted at Ala-Tur-DPro-Ser-NH for up to 60 minutes, and DAla-Tyr-DPro-Ser -NH 2 - up to 90 minutes.
- Met-Tyr-DPro-Ser-NH 2 did not significantly change the latent period of the tail withdrawal reaction.
- a change in amino acid residues around the Tur-Pro sequence affects analgesic activity.
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Abstract
La présente invention peut être utilisée dans le domaine de la physiologie et de la pharmacologie pour mettre au point de nouvelles préparations médicinales, ainsi qu'en médecine. L'invention se rapporte à la synthèse de peptides de formule générale (I), et à des peptides de formule générale A-B-Tyr-Pro (DPro, dHPro, DdHPro, DLdhPro, Hyp)-C-X, dans laquelle : A représente O, -Ala, -Asp, -Glu, -Phe, -His, -Ile, Lys, -Leu, -Met, -Pro, -Arg, -Ser, -Thr, -Val, -Trp, -Tyr; B représente O, -Ala, -Asp, -Glu, -Phe, -His, -Ile, Lys, -Leu, -Met, -Pro, -Arg, -Ser, -Thr, -Val, -Trp, -Tyr; C représente O, -Ala, -Asp, -Glu, -Phe, -His, -Ile, Lys, -Leu, -Met, -Pro, -Arg, -Ser, -Thr, -Val, -Trp, -Tyr; et X représente OH, -OCH3, -NH2. L'invention concerne également l'utilisation desdits peptides pour mettre au point de nouvelles préparations dotées d'une activité analgésique.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014021737A1 (fr) * | 2012-08-03 | 2014-02-06 | Tatyana Georgievna Emelyanova | Préparation pharmaceutique à base de dipeptide tyr-pro présentant une action anti-inflammatoire, antibactérienne et thérapeutique contre les blessures et les brûlures |
WO2022099123A1 (fr) * | 2020-11-06 | 2022-05-12 | The Medical College Of Wisconsin, Inc. | Inhibiteurs peptidiques de la protéine 1 de fission mitochondriale humaine et méthodes d'utilisation |
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WO2022099123A1 (fr) * | 2020-11-06 | 2022-05-12 | The Medical College Of Wisconsin, Inc. | Inhibiteurs peptidiques de la protéine 1 de fission mitochondriale humaine et méthodes d'utilisation |
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