(R)-4-((2-(1-(2-fluoro-6-(trifluoromethyl)benzyl)-2,4-dioxo-1'-((5-(trifluoromethyl)furan-2-yl)methyl)-1H-spiro[furo[3,4-d]pyrimidine-5,4'-piperidin]-3(2H,4H,7H)-yl)-1-phenylethyl)amino)butanoic acid | 1454272-94-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-4-((2-(1-(2-fluoro-6-(trifluoromethyl)benzyl)-2,4-dioxo-1'-((5-(trifluoromethyl)furan-2-yl)methyl)-1H-spiro[furo[3,4-d]pyrimidine-5,4'-piperidin]-3(2H,4H,7H)-yl)-1-phenylethyl)amino)butanoic acid
• 英文别名: (R)-4-((2-(1-(2-fluoro-6-(trifluoromethyl)benzyl)-2,4-dioxo-1′-((5-(trifluoromethyl)furan-2-yl)methyl)-1H-spiro[furo[3,4-d]pyrimidine-5,4′-piperidine]-3(2H,4H,7H)-yl)-1-phenylethyl)amino)butanoic acid；Merigolix；4-[[(1R)-2-[1-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-2,4-dioxo-1'-[[5-(trifluoromethyl)furan-2-yl]methyl]spiro[7H-furo[3,4-d]pyrimidine-5,4'-piperidine]-3-yl]-1-phenylethyl]amino]butanoic acid
• CAS: 1454272-94-6
• 化学式: C₃₆H₃₅F₇N₄O₆
• 分子量: 752.686
• InChiKey: LJPSGSMPGVITHK-MHZLTWQESA-N

物化性质

• 沸点：
  779.9±70.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  53
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  15

制备方法与用途

美利高是一种强效的促性腺激素释放激素（GnRH）拮抗剂。

反应信息

• 作为反应物：
  描述：

  (R)-4-((2-(1-(2-fluoro-6-(trifluoromethyl)benzyl)-2,4-dioxo-1'-((5-(trifluoromethyl)furan-2-yl)methyl)-1H-spiro[furo[3,4-d]pyrimidine-5,4'-piperidin]-3(2H,4H,7H)-yl)-1-phenylethyl)amino)butanoic acid 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以82%的产率得到
  参考文献：
  名称：

  퓨로피리미딘 화합물의 염 및 결정형, 및 이를 포함하는 약학적 조성물

  摘要：

  根据本发明的化学式1的化合物，即(R)-4-((2-(1-(2-氟-6-(三氟甲基)苄基)-2,4-二酮-1'-((5-(三氟甲基)呋喃-2-基)甲基)-1H-螺[呋喃[3,4-d]嘧啶-5,4'-哌啶]-3(2H,4H,7H)-基)-1-苯乙基)氨基)丁酮酸的盐和晶型在物理化学性质，如吸湿度，可塑性，化学稳定性等方面表现出优异，因此可方便地用于制备含有其作为有效成分的药用组合物。

  公开号：

  KR101973074B1

文献信息

• GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  申请人：SK CHEMICALS CO., LTD.

  公开号：US20150166558A1

  公开（公告）日：2015-06-18

  Disclosed are a gonadotropin releasing hormone receptor antagonist and a pharmaceutical composition including the same, which can be useful in preventing or treating a sex hormone-related disease such as endometriosis, amenorrhea, irregular menstruation, uterine myoma, uterine fibroids, polycystic ovarian disease, lupus erythematous, hypertrichosis, precocious puberty, short stature, acne, alopecia, gonadal steroid-dependent neoplasms, gonadotropin-producing pituitary adenoma, sleep apnea, irritable bowel syndrome, premenstrual syndrome, benign prostatic hyperplasia, contraception, and infertility, as well as Alzheimer disease.

  揭示了一种促性腺激素释放激素受体拮抗剂和包括该拮抗剂的药物组合物，可用于预防或治疗与性激素相关的疾病，如子宫内膜异位症、闭经、月经不调、子宫肌瘤、子宫纤维瘤、多囊卵巢综合征、红斑狼疮、多毛症、性早熟、身材矮小、痤疮、脱发、性腺类固醇依赖性肿瘤、促性腺激素产生垂体腺瘤、睡眠呼吸暂停、肠易激综合征、经前综合征、良性前列腺增生、避孕和不孕症，以及阿尔茨海默病。
• SALT AND CRYSTALLINE FORM OF FUROPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF
  申请人：TiumBio Co., Ltd.

  公开号：EP3889157A1

  公开（公告）日：2021-10-06

  Salts and crystalline forms of the compound of chemical formula 1, that is, (R)-4-((2-(1-(2-fluoro-6-(trifluoromethyl)benzyl)-2,4-dioxo-1'-((5-(trifluoromethyl)furan-2-yl)methyl)-1H-spiro[furo[3,4-d]pyrimidine-5,4'-piperidine]-3(2H,4H,7H)-yl)-1-phenylethyl)amino)butanoic acid according to the present invention are excellent in terms of general physicochemical properties, e.g., hygroscopicity, related substances, chemical stability, etc. and as such, can be utilized for pharmaceutical uses, such as the preparation of a pharmaceutical composition comprising same as an active ingredient.

  根据本发明的化学式1化合物，即(R)-4-((2-(1-(2-氟-6-(三氟甲基)苄基)-2,4-二氧代-1'-((5-(三氟甲基)呋喃-2-基)甲基)-1H-螺[呋喃并[3、4-d]嘧啶-5,4'-哌啶]-3(2H,4H,7H)-基)-1-苯乙基)氨基)丁酸。g.,吸湿性、相关物质、化学稳定性等，因此可用于医药用途，如制备包含本发明作为活性成分的药物组合物。
• US9481684B2
  申请人：——

  公开号：US9481684B2

  公开（公告）日：2016-11-01
• [EN] SALT AND CRYSTALLINE FORM OF PUROPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF<br/>[FR] SEL ET FORME CRISTALLINE D'UN COMPOSÉ DE PUROPYRIMIDINE ET UTILISATION PHARMACEUTIQUE ASSOCIÉE<br/>[KO] 퓨로피리미딘 화합물의 염 및 결정형, 및 이의 약학적 용도
  申请人：TIUMBIO CO LTD

  公开号：WO2020111524A1

  公开（公告）日：2020-06-04

  본 발명에 따른 화학식 1의 화합물, 즉 (R)-4-((2-(1-(2-플루오로-6-(트리플루오로메틸)벤질)-2,4-디옥소-1'-((5-(트리플루오로메틸)퓨란-2-일)메틸)-1H-스피로[퓨로[3,4-d]피리미딘-5,4'-피페리딘]-3(2H,4H,7H)-일)-1-페닐에틸)아미노)부타논산의 염 및 결정형은 물리화학적 제반 특성, 즉 흡습도, 유연물질, 화학적 안정성 등의 면에서 우수하여, 이를 유효 성분으로 포함하는 약학적 조성물의 제조와 같은 약학적 용도에 이용될 수 있다.
• [EN] SALT AND CRYSTALLINE FORM OF FUROPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF<br/>[FR] SEL ET FORME CRISTALLINE D'UN COMPOSÉ DE PUROPYRIMIDINE ET UTILISATION PHARMACEUTIQUE ASSOCIÉE<br/>[KO] 퓨로피리미딘 화합물의 염 및 결정형, 및 이의 약학적 용도
  申请人：TIUMBIO CO LTD

  公开号：WO2020111524A8

  公开（公告）日：2021-07-22

  [EN] Salts and crystalline forms of the compound of chemical formula 1, that is, (R)-4-((2-(1-(2-fluoro-6-(trifluoromethyl)benzyl)-2,4-dioxo-1'-((5-(trifluoromethyl)furan-2-yl)methyl)-1H-spiro[furo[3,4-d]pyrimidine-5,4'-piperidine]-3(2H,4H,7H)-yl)-1-phenylethyl)amino)butanoic acid according to the present invention are excellent in terms of general physicochemical properties, e.g., hygroscopicity, related substances, chemical stability, etc. and as such, can be utilized for pharmaceutical uses, such as the preparation of a pharmaceutical composition comprising same as an active ingredient.
  [FR] La présente invention concerne des sels et des formes cristallines du composé de formule chimique 1, c'est-à-dire de l'acide (R)-4-((2-(1-(2-fluoro-6-(trifluorométhyl)benzyl)-2,4-dioxo-1'-((5-(trifluorométhyl)furan-2-yl)méthyl)-1H-spiro[puro[3,4-d]pyrimidine-5,4'-pipéridine]-3(2H,4H,7H)-yl)-1-phényléthyl)amino)butanoïque qui présentent d'excellentes propriétés physico-chimiques générales, par exemple l'hygroscopicité, les substances associées, la stabilité chimique, etc. et en tant que tel, peuvent être utilisés pour des utilisations pharmaceutiques, telles que la préparation d'une composition pharmaceutique le comprenant en tant que principe actif.
  [KO] 본 발명에 따른 화학식 1의 화합물, 즉 (R)-4-((2-(1-(2-플루오로-6-(트리플루오로메틸)벤질)-2,4-디옥소-1'-((5-(트리플루오로메틸)퓨란-2-일)메틸)-1H-스피로[퓨로[3,4-d]피리미딘-5,4'-피페리딘]-3(2H,4H,7H)-일)-1-페닐에틸)아미노)부타논산의 염 및 결정형은 물리화학적 제반 특성, 즉 흡습도, 유연물질, 화학적 안정성 등의 면에서 우수하여, 이를 유효 성분으로 포함하는 약학적 조성물의 제조와 같은 약학적 용도에 이용될 수 있다.