Erythrocyte-stimulating factor mimic peptide derivative, medical salts thereof, preparation method and use thereof

A technology for erythropoietin and derivatives, applied in the field of erythropoietin mimetic peptide derivatives and pharmaceutically acceptable salts

Inactive Publication Date: 2009-06-17
JIANGSU HANSOH PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, these peptides have been greatly limited in clinical application. In order to overcome the deficiencies in the prior art, the present invention provides a kind of erythropoietin mimic peptide derivatives with better biological activity and higher bioavailability and their potential Medicinal salts and their preparation method

Method used

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  • Erythrocyte-stimulating factor mimic peptide derivative, medical salts thereof, preparation method and use thereof
  • Erythrocyte-stimulating factor mimic peptide derivative, medical salts thereof, preparation method and use thereof
  • Erythrocyte-stimulating factor mimic peptide derivative, medical salts thereof, preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] Example 1: Synthesis of Erythropoietin Mimetic Peptide Derivative Monomer Peptide

[0071] The synthesis of monomeric peptides of erythropoietin-mimetic peptide derivatives adopts the method of solid-phase peptide synthesis. This type of peptide synthesis method has been reported in many literatures. See stewart, J.M., and Young, J.D., solid phase peptide synthesis 2dedition, novabiochem peptide synthesis notes. The erythropoietin mimetic peptide derivative monomer peptide provided by the present invention adopts the method of manual synthesis, the resin is rink amind resin, and the α amino group of the amino acid derivative used is formed by Fmoc (fluorenyl carbonyl) Protection, cysteine ​​side chain sulfhydryl group, glutamine side chain amino group, histidine side chain imidazolyl group are protected by Trt (trityl), arginine side chain guanidine group is protected by Pbf(2,2,4, 6,7-pentamethyldihydrobenzofuran—5-sulfonyl) protection, tryptophan side chain indole gro...

Embodiment 2

[0072] Example 2: Preparation of functional small molecule (LG-1)

[0073]

[0074] Step 1: Preparation of LG-1-A

[0075]Dissolve diethyl iminodiacetate (10.0g, 52.8mmol), Boc-β-alanine (10.0g, 52.8mmol) in 100mL of dichloromethane, add DIC (8.0mL, 52.8mmol), Stir at room temperature overnight, filter, and the filtrate is successively washed with 100ml saturated NaHCO 3 , 50ml of 0.5N HCl solution, washed with 100ml of saturated brine, separated the organic layer, and the organic layer was washed with anhydrous MgSO 4 dry. Filter and concentrate to obtain LG-1-A as a colorless oily liquid: 17g.

[0076] Step 2: Preparation of LG-1-B

[0077] Dissolve 17 g of LG-1-A in 100 mL of MeOH: THF = 1:1 mixture, add 25 mL of water and 5 g of NaOH (125 mmol). After stirring at room temperature for 2 h, the pH value was adjusted to 1 with 6N HCl solution. Extracted 4 times with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and c...

Embodiment 3

[0082] Example Three: Preparation of Functional Small Molecules (LG-2)

[0083]

[0084] Dissolve 4g LG-1-B (13mmol) in 100mL N,N-dimethylformamide, add hydroxysuccinimide (3.1g, 21mmol), DIC (4mL, 26mmol) and DMAP (4-dimethyl Aminopyridine) (12mg, 0.08mmol). Stir overnight and concentrate under reduced pressure. The residue was dissolved in 80 ml of ethyl acetate, and the insoluble matter was filtered off. The organic phase was washed once with 40 ml of saturated sodium bicarbonate solution, 40 ml of saturated saline, 40 ml of 0.5N HCl solution, and 40 ml of saturated brine, and the organic layer was separated and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 4.4 g of white solid LG-2 (the yield was about 68%).

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Abstract

The invention relates to erythropoietin simulated peptide derivatives with a general formula (I) and medicinal use salts and a preparation method thereof, wherein R1, R2, R3, R4, R5, n1 and n2 are defined in an instruction book. The invention also relates to medicine compositions containing the erythropoietin simulated peptide derivatives with the general formula (I) and the medicinal use salts thereof. The erythropoietin simulated peptide derivatives with the general formula (I) and the medicinal use salts thereof, or the medicine compositions containing the erythropoietin simulated peptide derivatives with the general formula (I) and the medicinal use salts thereof can be widely applied to treating the diseases characterized by the deficiency of erythropoietin or the shortage or defect of erythrocyte groups.

Description

technical field [0001] The present invention relates to an erythropoietin mimetic peptide derivative and a pharmaceutically acceptable salt capable of binding to erythropoietin receptors and activating erythropoietin receptors or having an agonistic effect on erythropoietin, specifically, The present invention relates to an erythropoietin mimic peptide derivative modified by active methoxypolyethylene glycol and a preparation method thereof; A method for diseases characterized by absence or deficiency of red blood cell populations. technical background [0002] Erythropoietin (EPO) is a glycoprotein hormone with a molecular weight of about 34kD. Erythropoietin present in plasma is composed of 165 amino acids with a high degree of glycosylation, and the glycosyl component is mainly sialic acid. According to different carbohydrate content, naturally occurring erythropoietin is divided into two types, α-type and β-type, among which, α-type contains 34% carbohydrates, and β-ty...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/505A61K38/18A61P7/04A61P7/00A61P13/12A61P31/18A61P35/00A61P37/02A61P39/06A61P43/00
CPCA61K47/48215C07K14/505A61K47/481A61K47/55A61K47/60A61P7/06A61P11/00A61P13/12A61P25/00A61P31/18A61P35/00A61P37/02A61K47/50C07K17/08
Inventor 吕爱锋孙长安姜涛吴文涛王亚里
Owner JIANGSU HANSOH PHARMA CO LTD
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