| Identification | More | [Name]
Leuprorelin | [CAS]
53714-56-0 | [Synonyms]
5-OXOPRO-HIS-TRP-SER-TYR-D-LEU-LEU-ARG-PRO-NHC2H5
[DES-GLY10, DLEU6, PRO9]-LH-RH, ETHYL AMIDE
[DES-GLY10, DLEU6, PRO9]-LUTEINIZING HORMONE-RELEASING HORMONE, ETHYL AMIDE
[DES-GLY10, DLEU 6, PRONHET9]
(DES-GLY10,D-LEU6,PRO-NHET9)-GONADOTROPIN-RELEASING HORMONE
(DES-GLY10,D-LEU6,PRO-NHET9)-LHRH
[DES-GLY10, D-LEU6, PRO-NHET9]-LH-RH (HUMAN)
(DES-GLY10,D-LEU6,PRO-NHET9)-LUTEINIZING HORMONE-RELEASING FACTOR
(DES-GLY10,D-LEU6,PRO-NHET9)-LUTEINIZING HORMONE-RELEASING HORMONE
[DES-GLY10, D-LEU6, PRO-NHET9]-LUTEINIZING HORMONE-RELEASING HORMONE HUMAN
DES-GLY10,[P-LEU6]-LH-RH ETHYLAMIDE
GLP-HIS-TRP-SER-TYR-D-LEU-LEU-ARG-PRO-NHET
LEUPROLIDE
LEUPROLIDE ACETATE
LEUPROLIDE (HUMAN)
LEUPRORELIN
LEUPRORELIN ACETATE
LH-RH LEUPROLIDE
PGLU-HIS-TRP-SER-TYR-D-LEU-LEU-ARG-PRO-NHET
PGLU-HIS-TRP-SER-TYR-P-LEU-LEU-ARG-PRO-NHET | [EINECS(EC#)]
633-395-9 | [Molecular Formula]
C59H84N16O12 | [MDL Number]
MFCD00167544 | [Molecular Weight]
1209.4 | [MOL File]
53714-56-0.mol |
| Chemical Properties | Back Directory | [Appearance]
Hygroscopic, white or almost white powder. | [alpha ]
D25 -31.7° (c = 1 in 1% acetic acid) | [density ]
1.44±0.1 g/cm3(Predicted) | [storage temp. ]
−20°C
| [solubility ]
DMSO (Slightly), Methanol (Slightly), Water (Slightly) | [form ]
neat | [pka]
9.82±0.15(Predicted) | [Water Solubility ]
Soluble in water at 1mg/ml | [Stability:]
Hygroscopic | [InChIKey]
RGLRXNKKBLIBQS-VAZQWRJQNA-N | [Uses]
Gonadotropin releasing hormone (gonadorelin) analogue; treatment of prostate cancer. | [CAS DataBase Reference]
53714-56-0(CAS DataBase Reference) |
| Questions And Answer | Back Directory | [Description]
Leuprorelin(Leuprolide ) is a synthetic water-soluble nonapeptide with both ends closed, and also a highly active analogue of luteinizing hormone releasing hormone (LHRH or GnRH) produced by the hypothalamus. It can stimulate the pituitary gland to secrete gonadotropins and induce the production of steroids in the reproductive organs. | [Mechanism of action]
Leuprorelin is a nonapeptide synthetic analogue of Luteinizing Hormone Releasing Hormone (LHRH), which can promote the release of follicle stimulating hormone from the anterior pituitary, thereby reducing the increased testosterone concentration to castrate levels. When the administration is stopped, gonadotropins and androgens can return to normal concentrations. | [Uses]
Leuprorelin is a nonapeptide synthetic analogue of gonadotropin (GnRH), which can promote the release of luteinizing hormone (LHRH) and follicle stimulating hormone (FSH) from the anterior pituitary, regulate the secretion of gonadal hormones, and increase the serum levels of testosterone and dihydrotestosterone. Concentration, so as to achieve the function of treating reproductive system diseases. It is used to treat prostate cancer, uterine fibroids, ovarian cysts, breast cancer and cryptorchidism in children. | [Pharmacokinetics]
Leuprolide acetate(Leuprorelin) is ineffective orally. Good absorption by subcutaneous or intramuscular injection. A single subcutaneous injection of 3.75mg, the blood concentration of 1 to 2 days peaked at 1 to 2ng/ml. For prostate cancer, 3.75mg is injected subcutaneously each time, once every 4 Chemicalbook weeks, for a total of 3 injections, reaching a steady-state blood concentration of 0.1-1ng/ml. This product is hydrolyzed into 4 degradation products in the body and excreted by the kidneys. The urinary excretion rates of the original drug and metabolites were 2.9% and 1.5% after a single subcutaneous injection 28 days. | [Adverse reactions]
The main side effects of Leuprorelin are fever, heat sensation and elevated AST, ALT, γ-GTP and AKP. Sometimes there are facial flushing, sweating, loss of libido, impotence, feminized breasts, testicular atrophy, perineal discomfort and other endocrine system phenomena; abnormal electrocardiogram and increased ratio of heart and chest, bone pain, shoulder, lower back, limb pain, Urinary retention, frequent urination, hematuria, nausea, vomiting, loss of appetite, rash, itching and other allergic reactions and pain, induration, and redness at the injection site. Rarely, edema, chest pressure, chills, tiredness, weight gain, abnormal perception, tinnitus, hearing loss, TG, uric acid and BUN are increased. |
| Hazard Information | Back Directory | [Chemical Properties]
Hygroscopic, white or almost white powder. | [Originator]
Eligard,Atrix Laboratories, Inc. | [Definition]
ChEBI: An oligopeptide comprising pyroglutamyl, histidyl, tryptophyl, seryl, tyrosyl, D-leucyl, leucyl, arginyl, and N-ethylprolinamide residues joined in sequence. It is a synthetic nonapeptide analogue of gonadotropin-releasi
g hormone, and is used as a subcutaneous hydrogel implant (particularly as the acetate salt) for the treatment of prostate cancer and for the suppression of gonadal sex hormone production in children with central precocious puberty. | [Indications]
Leuprolide is a potent LH-RH agonist for the first
several days to a few weeks after initiation of therapy,
and therefore, it initially stimulates testicular and ovarian
steroidogenesis. Because of this initial stimulation of
testosterone production, it is recommended that patients
with prostatic cancer be treated concurrently with
leuprolide and the antiandrogen flutamide (discussed
earlier). Leuprolide is generally well tolerated, with hot
flashes being the most common side effect. | [Manufacturing Process]
5-Oxo-L-prolyl-L-histidyl-L-tryptophanyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-Larginyl-L-prolylethylamideacetate was prepared by using of Boc strategy on a
2%-crosslinking chloromethylated divinylbenzene-styrene copolymer in a the
Merrifield automatic sintesizer apparatus. 4.6 g of this resin/aminoacid
material is used for the synthesis of the desired nonapeptide. Each N-blocked
aminoacid is added in a three-fold access and allowed to couple to them,
existing aminoacid-resin ester in the usual coupling cycle. Ordinarily the
solvent used for the coupling reaction is dichloromethane or, when the
solubility of the blocked aminoacid is low, a mixture of dichloromethane and
DMF. Coupling is effected by the addition of a solution of
dicyclohexylcarbodiimide in dichloromethane at a 2.9 fold excess. The
sequence used for deprotection, neutralization and coupling of the next
aminoacid is done in a fully automatic system. In this manner, the peptide is
assembled using in turn Boc-Arg(Tos), Boc-Leu, Boc-D-Leu, Boc-Tyr(Cl2Bzl),
Boc-Ser(Bzl), Boc-Trp, Boc-His(DNP), and pGlu wherein all aminoacids are in
the L-form except in the leucine so designated. A 250 mg sample of the above
is placed in a hydrogen fluoride reaction with 250 mg vessel of anisole and
about 5 ml of anhydrous hydrogen fluoride is distilled into it. After 1 hour at
0°C, the hydrogen fluoride is removed with a stream of dry nitrogen and the
residue is taken up in 1% acetic acid. This solution is extracted with ether,
and the aqueous phase applied to a 1 time 30 cm column of a highly basic ion
exchange resin (marketed by Bio-Rad as AGl resin) in the acetate form. The
product is eluted with 0.1 N acetic acid and localized using thin-layer
chromatography (CHCl3/MeOH/32% HOAc: 120/90/40, silica gel G,
Cl2/tolidine). The product bearing solution is lyophilized, rechromatographed
on a Sephadex G-25 (marketed by Pharmacia of Uppsala, Sweden) column.
The product eluted is collected and lyophilized to yield a fluffy white solid. An
aminoacid analysis shows the expected ratio of all desired aminoacids
assembled in the above fashion. | [Therapeutic Function]
Antineoplastic | [Synthesis]
The synthesis process of Leuprorelin includes the following steps:
(1) Fmoc-Pro-HMPB-AM resin is obtained from Fmoc-Pro-OH and HMPB-AM resin with a substitution degree of 0.2mmol/g～1.2mmol/g as starting materials;
(2) The Fmoc-Pro-HMPB-AM resin was coupled one by one by Fmoc/tBu solid phase method to connect amino acids with protective groups in sequence, and the side chain fully protected leuprolide precursor peptide-HMPB-AM was synthesized Resin;
(3) Cut the side chain fully protected leuprolide precursor peptide-HMPB-AM resin to obtain the side chain fully protected leuprolide precursor peptide;
(4) Fully protected side chain leuprolide precursor peptide undergoes ethylamination to obtain side chain fully protected leuprolide;
(5) Leuprolide is fully protected on the side chain by removing the side chain protecting group to obtain the crude leuprolide peptide;
(6) The crude leuprorelin peptide is separated and purified by a high-pressure liquid phase column and lyophilized to obtain the leuprolide refined peptide. |
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