4-(3-(2-chlorophenyl)-4-(4-(1-propylazetidin-3-yloxy)phenyl)isoxazol-5-yl)-3-methylphenol 2,2,2-trifluoroacetate | 1383928-85-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3-(2-chlorophenyl)-4-(4-(1-propylazetidin-3-yloxy)phenyl)isoxazol-5-yl)-3-methylphenol 2,2,2-trifluoroacetate
• 英文别名: 4-[3-(2-Chlorophenyl)-4-[4-(1-propylazetidin-3-yl)oxyphenyl]-1,2-oxazol-5-yl]-3-methylphenol;2,2,2-trifluoroacetic acid
• CAS: 1383928-85-5
• 化学式: C₂HF₃O₂*C₂₈H₂₇ClN₂O₃
• 分子量: 589.011
• InChiKey: GFIOIKXVGHONKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.45
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  96
• 氢给体数：
  2
• 氢受体数：
  10

文献信息

• [EN] N-SUBSTITUTED AZETIDINE DERIVATIVES<br/>[FR] DÉRIVÉS D'AZÉTIDINE N-SUBSTITUÉS
  申请人：MSD OSS BV

  公开号：WO2012084711A1

  公开（公告）日：2012-06-28

  The present invention relates to novel N-substituted azetidine derivatives < of the formula (I); wherein SERMF is a Selective Estrogen Receptor Modilator fragment; X is no atom, O, S, CH2, carbonyl, N-R5; R1 is H, (C1 -8)alkyl, (C3-8)cycloalkyl, (C3-6)heterocycloalkyl, (C2-6)alkenyl, (C2- 6)alkynyl, (C1 -4)alkylcarbonyl, (C1 -4)alkoxy(C2-4)alkyl, (C3-6)cycloalkyl(C1 -3)- alkyl, (C3-6)heterocycloalkyl(C1 -3)alkyl, each independently optionally substituted with one or more halogen, nitrile, hydroxyl or (C1 -2)alkyl; R5 is H, (C1 -3)alkyl, optionally substituted with one or more fluorine; R17, R18 and R19 are independently of each other H, fluorine, nitrile or (C1 -3)- alkyl, optionally substituted with one or more fluorine; or a prodrug, isotopically-labelled derivative or pharmaceutically acceptable salt thereof, > to pharmaceutical compositions comprising these compounds and to their use in therapy, in particular to their use for the prevention or treatment of ovulatory dysfunction, uterine cancer, endometrium cancer, ovarian cancer, endometriosis, osteoporosis, prostate cancer, benign prostatic hypertrophy, and breast cancer, in particular ER-positive breast cancer, more in particular ER- positive, hormone treatment-resistant breast cancer. Said N-substituted azetidine derivatives have estrogen receptor alpha (ERa) antagonistic and - in certain embodiments - selective estrogen receptor downregulating (SERD) activity in ER-positive breast cancer cells.

  本发明涉及一种新型的N-取代氮杂环丙烷衍生物，其化学式为（I）；其中SERMF是选择性雌激素受体调节剂片段；X是无原子、O、S、CH2、酰基、N-R5；R1是H、（C1-8）烷基、（C3-8）环烷基、（C3-6）杂环烷基、（C2-6）烯基、（C2-6）炔基、（C1-4）烷基羰基、（C1-4）烷氧基（C2-4）烷基、（C3-6）环烷基（C1-3）烷基、（C3-6）杂环烷基（C1-3）烷基，每个独立地可选地被一个或多个卤素、腈基、羟基或（C1-2）烷基取代；R5是H、（C1-3）烷基，可选地被一个或多个氟原子取代；R17、R18和R19各自独立地是H、氟原子、腈基或（C1-3）烷基，可选地被一个或多个氟原子取代；或其前药、同位素标记衍生物或药用盐，用于包括这些化合物的药物组合物，以及它们在治疗中的使用，特别是用于预防或治疗排卵功能障碍、子宫癌、子宫内膜癌、卵巢癌、子宫内膜异位症、骨质疏松症、前列腺癌、良性前列腺增生和乳腺癌，特别是ER阳性乳腺癌，更具体地说是ER阳性、激素治疗耐药的乳腺癌。所述的N-取代氮杂环丙烷衍生物在ER阳性乳腺癌细胞中具有雌激素受体α（ERα）拮抗作用，而在某些情况下具有选择性雌激素受体下调（SERD）活性。
• N-SUBSTITUTED AZETIDINE DERIVATIVES
  申请人：Dijcks Fredericus Antonius

  公开号：US20160130262A1

  公开（公告）日：2016-05-12

  The present invention relates to novel N-substituted azetidine derivativesto pharmaceutical compositions comprising these compounds and to their use in therapy, in particular to their use for the prevention or treatment of ovulatory dysfunction, uterine cancer, endometrium cancer, ovarian cancer, endometriosis, osteoporosis, prostate cancer, benign prostatic hypertrophy, and breast cancer, in particular ER-positive breast cancer, more in particular ER-positive, hormone treatment-resistant breast cancer. Said N-substituted azetidine derivatives have estrogen receptor alpha (ERα) antagonistic and—in certain embodiments—selective estrogen receptor downregulating (SERD) activity in ER-positive breast cancer cells.

  本发明涉及新型N-取代的氮杂环丙烷衍生物，其化学式为(I)；其中SERMF是选择性雌激素受体调节剂片段；X是无原子，O，S，CH2，羰基，N—R5；R1是H，(C1-8)烷基，(C3-8)环烷基，(C3-6)杂环环烷基，(C2-6)烯基，(C2-6)炔基，(C1-4)烷基羰基，(C1-4)烷氧基(C2-4)烷基，(C3-6)环烷基(C1-3)-烷基，(C3-6)杂环环烷基(C1-3)烷基，每个独立地可选择地被一个或多个卤素，腈，羟基或(C1-2)烷基取代；R5是H，(C1-3)烷基，可选择地被一个或多个氟取代；R17，R18和R19各自独立地是H，氟，腈或(C1-3)-烷基，可选择地被一个或多个氟取代；或其前药、同位素标记衍生物或药学上可接受的盐，以及包含这些化合物的制药组合物和它们在治疗中的应用，特别是用于预防或治疗排卵功能障碍、子宫癌、子宫内膜癌、卵巢癌、子宫内膜异位症、骨质疏松症、前列腺癌、良性前列腺肥大和乳腺癌，特别是ER阳性乳腺癌，更特别是ER阳性，激素治疗耐药的乳腺癌。所述的N-取代的氮杂环丙烷衍生物在ER阳性乳腺癌细胞中具有雌激素受体α(ERα)拮抗和在某些实施例中选择性雌激素受体下调调节(SERD)活性。
• US9540361B2
  申请人：——

  公开号：US9540361B2

  公开（公告）日：2017-01-10