DEGARELIX

Base Information

• Chemical Name: DEGARELIX
• CAS No.: 214766-78-6
• Molecular Formula: C82H103ClN18O16
• Molecular Weight: 1632.28
• Mol file: 214766-78-6.mol

Synonyms:Acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide;Degarelix;Firmagon;D-Alaninamide, N-acetyl-3-(2-naphthalenyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridinyl)-D-alanyl-L-seryl-4-[[[(4S)-hexahydro-2,6-dioxo-4-pyrimidinyl]carbonyl]amino]-L-phenylalanyl-4-[(aminocarbonyl)amino]-D-phenylalanyl-L-leucyl-N6-(1-methylethyl)-L-lysyl-L-prolyl-;

Chemical Property of DEGARELIX

Chemical Property:

• PKA: 10.38±0.40(Predicted)
• PSA: 512.87000
• Density: 1.325 g/cm³
• LogP: 7.56580
• Storage Temp.: Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

Purity/Quality:

99%min ^*data from raw suppliers

Degarelix ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Antagonists of GnRH have proven to be an effective therapy for hormonally regulated cancers, such as prostate and some types of breast. As analogs of GnRH, they bind competitively and reversibly to GnRH receptors in the pituitary gland, thereby blocking the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In men, the reduction of LH triggers the ablation of testosterone secretion from the testes, and these castration-like levels have been essential in the effective management of advanced prostate cancer. In comparison to GnRH agonists, antagonists do not suffer from a potential flare of the disease as a result of an initial stimulation of the hypothalamic-pituitary-gonadal axis prior to down-regulation of the GnRH receptor. Moreover, GnRH antagonists provide beneficial effects more rapidly postdosing and result in a more efficient suppression of gonadotropin levels. With this in mind, degarelix acetate has been launched as a third-generation GnRH antagonist for the treatment of prostate cancer, and it joins other third-generation agents, ganirelix and cetronelix, on the market.
• Uses: Degarelix, is a competitive and reversible gonadotropin-releasing hormone receptor (GnRHR) antagonist. Advanced hormone-dependent prostate carcinoma
• Clinical Use: Ferring launched degarelix acetate, a gonadotrophin-releasing hormone (GnRH) antagonist, in 2009 in the U.S. for the treatment of prostate cancer. The compound has been approved by the E.U. for the same indication, and in the same year it was launched in the UK and Germany. Degarelix has been developed as a one-month or three-month sustained-release injectable formulation. Compared to other GnRH antagonists, degarelix displays improved aqueous solubility, longer acting effects and weaker histamine-releasing properties.
• Drug interactions: Potentially hazardous interactions with other drugsNone known

Technology Process of DEGARELIX

There total 5 articles about DEGARELIX which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 67.0%

Fmoc-Rink resin + Fmoc-Leu-OH (35661-60-0) + Fmoc-L-Lys(iPr,Boc)-OH (201003-48-7) + 9-fluorenylmethyloxycarbonyl-N(4)-(L-hydroorotyl)-4-aminophenylalanine + Fmoc-Pro-OH (71989-31-6) + Fmoc-Ser(tBu)-OH (71989-33-8) + acetic anhydride (108-24-7) + N-(9-fluorenylmethoxycarbonyl)-D-alanine (35661-38-2,35661-39-3,79990-15-1,136132-75-7) + N-[(9-fluorenyl)methoxycarbonyl]-3-(2-naphthyl)-D-alanine (138774-94-4,186320-03-6) + 9-fluorenylmethyloxycarbonyl-D-4-chlorophenylalanine + Nα-(fluorenylmethyloxycarbonyl)-p-ureido-D-phenylalanine + (R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(pyridin-3-yl)propanoic acid (175453-07-3,142994-45-4) → acetyl-3-(naphthalen-2-yl)-D-alanyl-4-chloro-D-phenylalanyl-3-(pyridin-3-yl)-D-alanyl-Ser-4-((((4S)-2,6-dioxohexahydropyrimidin-4-yl)carbonyl)amino)-L-phenylalanyl-4-(carbamoylamino)-D-phenylalanyl-Leu-N6-(1-methylethyl)-L-lysyl-Pro-D-Ala-NH2 (214766-78-6)

Guidance literature:

Fmoc-Rink resin; With tert-butylamine; In N,N-dimethyl-formamide; Rink amide resin

N-(9-fluorenylmethoxycarbonyl)-D-alanine; With diisopropyl-carbodiimide; In N,N-dimethyl-formamide; for 1h; Rink amide resin

Fmoc-Leu-OH; Fmoc-L-Lys(iPr,Boc)-OH; 9-fluorenylmethyloxycarbonyl-N⁽⁴⁾-(L-hydroorotyl)-4-aminophenylalanine; Fmoc-Pro-OH; Fmoc-Ser(tBu)-OH; acetic anhydride; N-[(9-fluorenyl)methoxycarbonyl]-3-(2-naphthyl)-D-alanine; 9-fluorenylmethyloxycarbonyl-D-4-chlorophenylalanine; N^α-(fluorenylmethyloxycarbonyl)-p-ureido-D-phenylalanine; (R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(pyridin-3-yl)propanoic acid; Further stages;

DOI:10.1021/acs.oprd.9b00540

Reference yield:

C148H217ClN18O20 → acetyl-3-(naphthalen-2-yl)-D-alanyl-4-chloro-D-phenylalanyl-3-(pyridin-3-yl)-D-alanyl-Ser-4-((((4S)-2,6-dioxohexahydropyrimidin-4-yl)carbonyl)amino)-L-phenylalanyl-4-(carbamoylamino)-D-phenylalanyl-Leu-N6-(1-methylethyl)-L-lysyl-Pro-D-Ala-NH2 (214766-78-6)

Guidance literature:

With chlorotriisopropylsilane; trifluoroacetic acid; In water; at 20 ℃; for 2h; Cooling with ice;

DOI:10.1002/anie.201702931

Reference yield:

C97H114ClN18O18Pol → acetyl-3-(naphthalen-2-yl)-D-alanyl-4-chloro-D-phenylalanyl-3-(pyridin-3-yl)-D-alanyl-Ser-4-((((4S)-2,6-dioxohexahydropyrimidin-4-yl)carbonyl)amino)-L-phenylalanyl-4-(carbamoylamino)-D-phenylalanyl-Leu-N6-(1-methylethyl)-L-lysyl-Pro-D-Ala-NH2 (214766-78-6)

Guidance literature:

With hydrogen fluoride; methoxybenzene; MBHA resin

DOI:10.1002/psc.2678

upstream raw materials:

Fmoc-Ser(tBu)-OH

acetic anhydride

N-[(9-fluorenyl)methoxycarbonyl]-3-(2-naphthyl)-D-alanine

(R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(pyridin-3-yl)propanoic acid

Refernces

• 1、 Zhou, Ning,Gao, Xing,Lv, Yujian,Cheng, Junping,Zhou, Wenxia,Liu, Keliang. "Self-assembled nanostructures of long-acting GnRH analogs modified at position 7". . p. 868 - 875. Retrieved 2014.
• 2、 Takahashi, Daisuke,Inomata, Tatsuji,Fukui, Tatsuya. "AJIPHASE: A Highly Efficient Synthetic Method for One-Pot Peptide Elongation in the Solution Phase by an Fmoc Strategy". . p. 7803 - 7807. Retrieved 2017/06/27.