65807-02-5

• 常用中文名：戈舍瑞林
• 常用英文名：Goserelin
• CAS号：65807-02-5
• 分子式：C₅₉H₈₄N₁₈O₁₄
• 分子量：1269.41
• 相关类别： 原料药 激素及调节内分泌功能类药 促性激素类药
• 发布时间：2018-02-05 08:00:00
• 更新时间：2026-07-18 13:50:32
• 【用途1】
  为合成的促性腺激素释放激素的类似物，较天然的促性腺激素释放激素强50-100倍。用于内分泌疗法的晚期前列腺癌。
• 本药是一种合成的、促黄体生成素释放激素的类似物，长期使用可抑制垂体的促黄体生成激素的分泌，从而引起男性血清睾酮和女性血清雌二醇的下降，停药后这一作用是可逆的。 男性病人在第一次用药之后21日左右，睾酮浓度可降低到去势后的水平，在每28天用药1次的治疗过程中，睾酮浓度一直保持在去势后的浓度范围内。这种睾酮抑制作用可使大多数病人的前列腺肿瘤消退，症状改善。 女性患者在初次用药后21日左右，血清雌二醇浓度受到抑制，并在以后每28天的治疗中维持在绝经后水平。这种抑制与激素依赖性的乳腺癌，子宫内膜异位症相关。药代动力学：本药具有几乎完全的生物利用度。每4周使用一注射埋植剂，可保持有效血药浓度，而无组织蓄积。诺雷德的蛋白结合能力较差，在肾功能正常的情况下，血浆清除半衰期为2-4小时，肾功能不全病人的半衰期将会延长，但对于每月都使用埋植剂的患者来说，这影响非常小，故没有必要改变这些病人的用量。在肝功能不全的病人中，药代动力学无明显的变化。毒理研究：在长期重复使用诺雷德的雄性鼠中，曾观察到良性脑垂体肿瘤的发病率上升，这一事实与以前已观察到的行外科去势后的大鼠的情形相似，但尚未发现与人体使用的经验有任何关联。在小鼠实验中，长期重复使用数倍于人类常用剂量的诺雷德后，可发现胰岛细胞及幽门部胃粘膜细胞增生。这些事实与临床的关系尚不清楚。适应症：适用于可用激素治疗的前列腺癌及绝经前和绝经期的乳腺癌。子宫内膜异位症。用量用法：成人 3.6 mg的注射埋植剂，每28日1次，作腹前壁皮下注射，如果必要可使用局部麻醉。肝、肾功能不全者或老年病人不必调整剂量。子宫内膜异位症病人的疗程为6个月。 不良反应 曾有报道出现皮疹，常不需中断治疗即可恢复。偶见皮下注射部位的轻度肿胀。男性病人可见潮红及性欲减退，偶见乳房肿胀和硬结。前列腺癌病人用药初期可见暂时性骨骼疼痛加剧，可行对症治疗。个别病例可见尿道梗阻和脊髓压迫。女性病人可见潮红，出汗及性欲减退，一般不需停药。也可见头痛及情绪变化如抑郁。曾见阴道干燥及乳房体积改变。乳腺癌的病人，用药初期会有症状加剧。极少数患子宫内膜异位症的病人，使用促黄体生成素释放激素类似物后发生停经，而停药后月经不再来潮。 禁忌症 已知对促黄体生成素释放激素类似物过敏的病人，妊娠及哺乳妇女不可使用本品。

名称

• 中文名: 戈舍瑞林
• 英文名: Goserelin
• 中文别名: 3-[焦谷氨酰组氨酰色氨酰丝氨酰醋氨酰(3-O-叔丁基)-D丝氨酰亮氨酰精氨酰脯氨酰]肼基甲酰胺; 戈舍瑞林杂质D7; 戈舍瑞林-D7三氟乙酸盐; 果丝瑞宁; 戈舍瑞林 标准品; 醋酸戈舍瑞林 标准品; 高舍瑞林; 性瑞林; 戈舍瑞林-D7; 戈舍瑞林NMR鉴定 标准品; 戈舍瑞林-D5; 戈舍瑞林(GOSERELIN); 戈舍瑞林中间体; 胺碘酮盐酸盐杂质E
• 英文别名: Einecs -4; Goserelin/Zoladex/Decaptide I; (D-SER(TBU)6,AZAGLY10)-LHRH ACETATE SALT; 5-Oxo-L-prolyl-L-histidyl-N-[(1S,4S,7R,10S,13S)-18-amino-13-({(2S)-2-[(2-carbamoylhydrazino)carbonyl]-1-pyrrolidinyl}carbonyl)-4-(4-hydroxybenzyl)-1-(hydroxymethyl)-18-imino-10-isobutyl-7-{[(2-methyl-2-propanyl)oxy]methyl}-2,5,8,11-tetraoxo-3,6,9,12,17-pentaazaoctadec-1-yl]-L-tryptophanamide; (2S)-N-[(1S,4S,7S,10S,13R,16S,19S)-24-amino-13-(tert-butoxymethyl)-19-({(2S)-2-[(2-carbamoylhydrazino)carbonyl]pyrrolidin-1-yl}carbonyl)-10-(4-hydroxybenzyl)-7-(hydroxymethyl)-1-(1H-imidazol-4-ylmethyl)-24-imino-4-(1H-indol-3-ylmethyl)-16-(2-methylpropyl)-2,5,8,11,14,17-hexaoxo-3,6,9,12,15,18,23-heptaazatetracos-1-yl]-5-oxopyrrolidine-2-carboxamide; Sodium alpha-(3,5-dibromo-2-methyl-4-oxo-2,5-cyclohexadienylidene)-alpha-(3,5-dibromo-4-hydroxyphenyl)toluenesulphonate; Goserelin (free base); Phenol, 4,4'-(2,2-dioxido-3H-1,2-benzoxathiol-3-ylidene)bis(2,6-dibromo-3-methyl-, sodium salt (1:1); Goserelin-d7; GOSERELIN ACETATE PH. EUR; Pyr-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-g-Pro-Azagly-Gly-NH2; (2S)-N-[(1S,4S,7S,10S,13R,16S,19S)-24-amino-13-(tert-butoxymethyl)-19-({(2S)-2-[(2-carbamoylhydrazino)carbonyl]pyrrolidin-1-yl}carbonyl)-10-(4-hydroxybenzyl)-7-(hydroxymethyl)-1-(1H-imidazol-4-ylmethyl)-24-imino-4-(1H-indol-3-ylmethyl)-16-(2-methylpropyl)-2,5,8,11,14,17-hexaoxo-3,6,9,12,15,18,23-heptaazatetracos-1-yl]-5-oxopyrrolidine-2-carboxamide (non-preferred name); Goserelin Deuterated Acetate DISCONTINUED; Goserelin for NMR identification CRS; 5-Oxo-L-Pro-L-His-L-Trp-L-Ser-L-Tyr-O-(1,1-dimethylethyl)-D-Ser-L-Leu-L-g-L-Pro-ureido-NH2; (2S)-N-[(1S,4S,7S,10S,13R,16S,19S)-24-Amino-13-(tert-butoxymethyl)-19-({(2S)-2-[(2-carbamoylhydrazino)carbonyl]pyrrolidin-1-yl}carbonyl)-10-(4-hydroxybenzyl)-7-(hydroxymethyl)-1-(1H-imidazol-4-ylmethyl)-24-imino-4-(1H-indol-3-ylmethyl)-16-(2-methylpropyl)-2,5,8,11,14,17-hexaoxo-3,6,9,12,15,18,23-heptaazatetracos-1-yl]-5-oxopyrrolidin-2-carboxamid; Geserelin; Goserelin-d7Q: What is Goserelin-d7 Q: What is the CAS Number of Goserelin-d7; Goserelin validation mixture CRS; Luteinizing hormone-releasing factor (swine), 6-[O-(1,1-dimethylethyl)-D-serine]-, 2-(aminocbonyl)hydrazide; (2S)-N-[(1S,4S,7S,10S,13R,16S,19S)-24-amino-19-({(2S)-2-[(2-carbamoylhydrazino)carbonyl]pyrrolidin-1-yl}carbonyl)-13-[(1,1-diméthyléthoxy)méthyl]-10-(4-hydroxybenzyl)-7-(hydroxyméthyl)-1-(1H-imidazol-4-ylméthyl)-24-imino-4-(1H-indol-3-ylméthyl)-16-(2-méthylpropyl)-2,5,8,11,14,17-hexaoxo-3,6,9,12,15,18,23-heptaazatétracos-1-yl]-5-oxopyrrolidine-2-carboxamide; Goserelin D10Q: What is Goserelin D10 Q: What is the CAS Number of Goserelin D10 Q: What is the storage condition of Goserelin D10 Q: What e the applications of Goserelin D10; (D-SER(TBU)6,AZAGLY10)-LUTEINIZING HORMONE-RELEASING HORMONE ACETATE SALT; ici118630; Zoladex; (D-SER(TBU)6,AZAGLY10)-LUTEINIZING HORMONE-RELEASING FACTOR ACETATE SALT; 1-(5-Oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-O-tert-butyl-D-seryl-L-leucyl-L-arginyl-L-prolyl)semicarbazide; (2S)-N-[(2S,5S,8S,11S,14R,17S,20S)-25-Amino-14-(tert-butoxymethyl)-20-({(2S)-2-[(2-carbamoylhydrazino)carbonyl]pyrrolidin-1-yl}carbonyl)-11-(4-hydroxybenzyl)-8-(hydroxymethyl)-1-(1H-imidazol-4-yl)-25-imino-5-(1H-indol-3-ylmethyl)-17-isobutyl-3,6,9,12,15,18-hexaoxo-4,7,10,13,16,19,24-heptaazapentacosan-2-yl]-5-oxopyrrolidine-2-carboxamide (non-preferred name); (D-Ser(tBu)6,Azagly10)-LHRH (free base); Goserelin CRS; Decapeptide I; GOSERELIN ACETATE SALT; endo-5a-glycine-gonadorelin; Gosereline; PYR-HIS-TRP-SER-TYR-D-SER(TBU)-LEU-G-PRO-AZAGLY-NH2 ACETATE SALT; decaptidei; luteinizinghormone-releasingfactor(pig),6-(o-1,1-dimethylethyl)-d-serene)-1; Goserelin Acetate(net); 6-[O-(1，1-Dimethylethyl)-D-serine]-10-deglycirmmideluteinizing hormone-releasing factor(pig)2-(aminocbonyl)hydrazide; d-ser(t-bu)(sup6)aza-gly(sup10)-gnrh; Goserelin //BP; Goserelin, Gosereline, Goserelinum, Goserelina; Human Goserelin; (D-SER(TBU)6,AZAGLY10)-GONADOTROPIN-RELEASING HORMONE ACETATE SALT; (2S)-N-[(2S,5S,8S,11S,14R,17S,20S)-25-amino-14-(tert-butoxymethyl)-20-({(2S)-2-[(2-carbamoylhydrazinyl)carbonyl]pyrrolidin-1-yl}carbonyl)-11-(4-hydroxybenzyl)-8-(hydroxymethyl)-1-(1H-imidazol-4-yl)-25-imino-5-(1H-indol-3-ylmethyl)-17-(2-methylpropyl)-3,6,9,12,15,18-hexaoxo-4,7,10,13,16,19,24-heptaazapentacosan-2-yl]-5-oxopyrrolidine-2-carboxamide (non-preferred name); Goserlin; Goserelin-d7 Tritrifluoroacetate; 2-(aminocbonyl)hydrazide; Pbtbo; Luteinizing hormone-releasing factor (pig), 6-[O-(1,1-dimethylethyl)-D-serine]-10-deglycinamide-, 2-(aminocbonyl)hydrazide

物化性质

• 密度: 1.5±0.1 g/cm3
• 分子式: C₅₉H₈₄N₁₈O₁₄
• 分子量: 1269.41
• PSA: 493.39000
• LogP: -0.95
• 外观性状: 白色固体
• 折射率: 1.692
• 储存条件: −20°C
• 水溶解性: H2O: 20 mg/mL, clear, colorless

生物活性

• 描述: Goserelin(ICI 118630)是注射型促性腺激素释放激素(GnRH)超激动剂。
• 相关类别:
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> GNRH受体
  研究领域 >> 内分泌
• 参考文献:

  [1]. Goserelin, From Wikipedia

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : OK6369800 CHEMICAL NAME : Luteinizing hormone-releasing factor (pig), 6-(O-1,1-dimethylethyl)-D-serene)-10- deglycinamide-, 2-(aminocarbonyl)hydrazide CAS REGISTRY NUMBER : 65807-02-5 LAST UPDATED : 199510 DATA ITEMS CITED : 3 MOLECULAR FORMULA : C59-H84-N18-O14 MOLECULAR WEIGHT : 1269.61 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Human - man DOSE/DURATION : 51 ug/kg TOXIC EFFECTS : Brain and Coverings - changes in circulation (hemorrhage, thrombosis, etc.) Sense Organs and Special Senses (Eye) - diplopia Nutritional and Gross Metabolic - other changes REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 345,458,1995 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 12 mg/kg SEX/DURATION : male 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands REFERENCE : JOAND3 Journal of Andrology. (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1980- Volume(issue)/page/year: 10,478,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 12 mg/kg SEX/DURATION : male 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - other effects on male Endocrine - androgenic REFERENCE : JOAND3 Journal of Andrology. (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1980- Volume(issue)/page/year: 10,478,1989

安全

• 安全声明 (欧洲): S22-S24/25
• WGK德国: 3

制备

【方法1】
0.2mmol 5-oxoPro-His-NHNH2悬浮于0.9ml二甲基甲酰胺和0.7ml二甲亚砜的混合溶剂中，在0℃和搅拌下，加入0.8mmol 5.7mol/L盐酸的二氧六环溶液，剧烈搅拌5min，得到澄清的溶液。冷至-20℃，加入0.22mmol亚硝酸叔丁酯，再搅拌25min。冷至-30℃，加入0.8mmol三乙胺来中和。加人冷至-20℃的0.1mmol的L-Trp-Ser-Tyr-D-Ser(t-Bu)-Leu-Arg-PrcrNHNHCONH2二盐酸盐和0.1mmol三乙胺溶于lml二甲基甲酰胺的溶液，然后在4℃下搅拌24h。减压蒸出溶剂，剩余物用Sephadex LH-20进行柱层析，用二甲基甲酰胺洗脱。然后用SephadexG-25来提纯，用正丁醇：乙酸：水：吡啶=5：1：5：1(体积比)来洗脱，可得产物。