Goserelin Chemical Properties

Density 

1.50±0.1 g/cm3(Predicted)

storage temp. 

−20°C

solubility 

H₂O: 20 mg/mL, clear, colorless

form 

white powder

pka

9.82±0.15(Predicted)

InChI

InChI=1S/C59H84N18O14/c1-31(2)22-40(49(82)68-39(12-8-20-64-57(60)61)56(89)77-21-9-13-46(77)55(88)75-76-58(62)90)69-54(87)45(29-91-59(3,4)5)74-50(83)41(23-32-14-16-35(79)17-15-32)70-53(86)44(28-78)73-51(84)42(24-33-26-65-37-11-7-6-10-36(33)37)71-52(85)43(25-34-27-63-30-66-34)72-48(81)38-18-19-47(80)67-38/h6-7,10-11,14-17,26-27,30-31,38-46,65,78-79H,8-9,12-13,18-25,28-29H2,1-5H3,(H,63,66)(H,67,80)(H,68,82)(H,69,87)(H,70,86)(H,71,85)(H,72,81)(H,73,84)(H,74,83)(H,75,88)(H4,60,61,64)(H3,62,76,90)/t38-,39-,40-,41-,42-,43-,44-,45+,46-/m0/s1

InChIKey

BLCLNMBMMGCOAS-URPVMXJPSA-N

SMILES

CC(C[C@@H](C(N[C@H](C(N1[C@H](C(NNC(=O)N)=O)CCC1)=O)CCC/N=C(/N)\N)=O)NC([C@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@H]1NC(=O)CC1)=O)CC1NC=NC=1)=O)CC1C2C(=CC=CC=2)NC=1)=O)CO)=O)CC1C=CC(O)=CC=1)=O)COC(C)(C)C)=O)C

Safety Information

Safety Statements 

22-24/25

WGK Germany 

3

HS Code 

3504009000

Hazardous Substances Data

65807-02-5(Hazardous Substances Data)

MSDS

• Language:English Provider:SigmaAldrich

Goserelin Usage And Synthesis

Description

Goserelin is an analog of luteinizing hormone-releasing hormone (LHRH) useful in the treatment of malignancies responsive to hormonal manipulation. Administered parenterally in a biodegradable depot, goserelin is reportedly as effective as orchidectomy and oophorectomy in patients with advanced prostate carcinoma and pre-menopausal breast cancer.

Chemical Properties

White or almost white powder.

Originator

ICI (United Kingdom)

Uses

Goserelin USP (Zoladex) is used to treat Prostatic carcinoma.

Uses

Labeled Goserelin, intended for use as an internal standard for the quantification of Goserelin by GC- or LC-mass spectrometry.

Uses

Labelled Goserelin (G767500). Synthetic peptide agonist analog of LH-RH. Antineoplastic (hormonal).

Definition

ChEBI: Goserelin is an organic molecular entity.

Manufacturing Process

(a) Solid Phase Preparation of Nonapeptide
The solid phase synthesis was carried out in automatic mode on an Applied Biosystems 430A Peptide Synthesizer using Boc-Pro-OBzl-polystyrene resin 1% cross-linked with divinylbenzene (Peninsula Laboratories), 1.25 g, 0.38 meq/g though nominally 0.7 meq/g). The following protected amino acids were converted to benzotriazolyl esters by reaction with HOBt (1- hydroxybenzotriasole) and DIPC (di-isopropylcarbodiimide) in DMF immediately before use. The protected amino acids were coupled in the following sequence: Boc-Arg(HCl)-OH; Boc-Leu-OH; Fmoc-D-Ser(But)-OH; Fmoc-Tyr(BrZ)-OH; Fmoc-Ser-OH; Fmoc-Trp-OH; Fmoc-His(Fmoc)-OH; PyrOH. The sequence of operations for the first two stages (using Boc-protectedamino acids) was: removal of Boc with 45% triflouroacetic acid in dichloromethane;10% DIEA (diethyl amine)/DMF wash; coupling (2 equivalents of protected amino acid HOBt ester); removal of Boc as above. The sequence of operations for the last six stages (using Fmoc-protectedamino acids) was: removal of Fmoc with 20% piperidine/DMF; 0.5 molar HOBt/DMF wash; coupling (1 equivalent of protected amino acid HOBt ester). All coupling reactions except that using Boc-Arg(HCl)-OH were of 1 hour duration; the Boc-Arg(HCl)-OH one was of 2 hours duration. There was thus obtained the nonapeptide-resin (1.7 g; 0.29 mmole peptide per g) with the Tyr still protected by BrZ.
(b) Cleavage of Peptide From Resin
The peptide resin prepared above was treated with a 20-fold excess of anhydrous hydrazine in DMF (20 ml) at laboratory temperature for 24 hours, and the mixture was filtered and evaporated to dryness. This procedure also removed the BrZ protecting group from the Tyr moeity. The residue was purified by gel filtration on a column (LH 20 Sephadex) using a 20:1 v/v mixture of water and acetic acid as eluant. There was thus obtained Pyr-HisTrp-Ser-Tyr-D-Ser(But)-Leu-Arg(H+)-Pro-NH-NH2. The structure of which was confirmed by amino acid analysis and mass spectroscopy.
(c) Preparation of Goserelin
A solution of potassium cyanate (11 mg) in water (1.36 ml) was added portionwise during 1 hour to a solution of the above hydrazide (118 mg) in a 20:1 v/v mixture of water and acetic acid (10 ml). The mixture was freezedried and the residue was purified by reverse-phase column chromatography (Dynamax 60 ANG, C18, 1 inch diameter) using a gradient of 10% to 40% by volume of acetonitrile in water containing 0.1% trifluoroacetic acid. There was thus obtained goserelin (100 mg, 25% yield overall), the structure of which was confirmed by mass spectroscopy.

brand name

Zoladex (Zeneca).

Therapeutic Function

Antineoplastic, Antitumor

Clinical Use

Synthetic decapeptide analogue of LHRH:

Treatment of advanced prostate cancer, breast cancer, endometriosis and endometrial thinning and uterine fibroids

Side effects

Hot flashes (flushing), dizziness, headache, increased sweating, decreased sexual interest/ability, trouble sleeping, nausea, change in breast size, vaginal dryness, or hair loss may occur. Pain, bruising, bleeding, redness, or swelling at the injection site may also occur.
This medication may rarely make your blood sugar rise, which can cause or worsen diabetes.
Serious side effects including: symptoms of a heart attack (such as chest/jaw/left arm pain, shortness of breath, unusual sweating), signs of a stroke (such as weakness on one side of the body, trouble speaking, sudden vision changes, confusion), fast/irregular heartbeat, severe dizziness, fainting.
In men using this medication for prostate cancer, a rare but very serious urinary blockage problem or spinal cord problem (compression) can occur, especially during the first month of treatment.

Drug interactions

Goserelin may be given on its own or is often combined with another hormone therapy such as tamoxifen or drugs known as aromatase inhibitors (anastrozole, exemestane and letrozole).
The risk or severity of QTc prolongation can be increased when Goserelin is combined with Clozapine. The risk or severity of methemoglobinemia can be increased when Goserelin is combined with Cocaine.

Metabolism

Metabolised by tissue peptidases and is excreted in urine and bile as unchanged drug and metabolites.

Goserelin(65807-02-5)Related Product Information

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