17β-hydroxy-7α-{13-(4,4,5,5,5-pentafluoropentylsulfanyl)tridecyl}-5α-androstan-3-one | 326858-80-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 17β-hydroxy-7α-{13-(4,4,5,5,5-pentafluoropentylsulfanyl)tridecyl}-5α-androstan-3-one
• 英文别名: 17β-hydroxy-7α-{13-(4,4,5,5,5-pentafluoro-pentylsulfanyl)tridecyl}-5α-androstan-3-one；(5S,7R,8R,9S,10S,13S,14S,17S)-17-hydroxy-10,13-dimethyl-7-[13-(4,4,5,5,5-pentafluoropentylsulfanyl)tridecyl]-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-one
• CAS: 326858-80-4
• 化学式: C₃₇H₆₁F₅O₂S
• 分子量: 664.948
• InChiKey: ZYHMYUHWNWGQBP-CSLZCNNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.7
• 重原子数：
  45
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  17β-hydroxy-7α-{13-(4,4,5,5,5-pentafluoropentylsulfanyl)tridecyl}-5α-androstan-3-one 在 Oxone 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 以73%的产率得到17β-hydroxy-7α-{13-(4,4,5,5,5-pentafluoropentylsulfinyl)tridecyl}-5α-androstan-3-one
  参考文献：
  名称：

  Discovery of 7α-substituted dihydrotestosterones as androgen receptor pure antagonists and their structure–activity relationships

  摘要：

  A series of 7 alpha-substituted dihydrotestosterone derivatives were synthesized and evaluated for androgen receptor (AR) pure antagonistic activity. From reporter gene assay (RGA), the compound with a side chain containing N-n-butyl-N-methyl amide (19a) showed pure antagonistic activity (IC50 = 340 nM, FI5 > 10,000 nM), whereas known AR antagonists showed partial agonistic activities. The optimization of 19a led to compound 23 (CH4892280), which showed more potent pure antagonistic activity (IC50 = 190 nM, FI5 > 10,000 nM). The SARs of tested compounds suggested that the length of the side chain and the substituents on the amide nitrogen are important for pure antagonistic activities. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.072
• 作为产物：
  描述：

  17β-hydroxy-7α-(2-propen-1-yl)-5α-androstan-3-one 在 palladium on activated charcoal 、 Grubbs catalyst first generation 盐酸 、 氢气 、 sodium methylate 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 丙酮 为溶剂， 反应 55.0h， 生成 17β-hydroxy-7α-{13-(4,4,5,5,5-pentafluoropentylsulfanyl)tridecyl}-5α-androstan-3-one
  参考文献：
  名称：

  Discovery of 7α-substituted dihydrotestosterones as androgen receptor pure antagonists and their structure–activity relationships

  摘要：

  A series of 7 alpha-substituted dihydrotestosterone derivatives were synthesized and evaluated for androgen receptor (AR) pure antagonistic activity. From reporter gene assay (RGA), the compound with a side chain containing N-n-butyl-N-methyl amide (19a) showed pure antagonistic activity (IC50 = 340 nM, FI5 > 10,000 nM), whereas known AR antagonists showed partial agonistic activities. The optimization of 19a led to compound 23 (CH4892280), which showed more potent pure antagonistic activity (IC50 = 190 nM, FI5 > 10,000 nM). The SARs of tested compounds suggested that the length of the side chain and the substituents on the amide nitrogen are important for pure antagonistic activities. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.072

文献信息

• ANTIANDROGEN AGENTS
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1219631A1

  公开（公告）日：2002-07-03

  Compounds represented by the general formula (I), pharmaceutically acceptable salts thereof, or prodrugs of the compounds or their salts: [wherein X1 and X2 represent independently a hydrogen atom or a group represented by the general formula (II)         -Ar-A-R1     (II) Ra represents a hydrogen atom or a protective group of a hydroxyl group, Rb and Rc, when taken together with the carbon atom in 3-position to which they are bound, represent an optionally protected -(C=O)-, and the dashed line in combination with the solid line represents the formation of a single bond or a double bond;    in addition, Ar represents a single bond or an aromatic hydrocarbon group, A represents a methylene group or -O-, R1 represents an optionally substituted alkyl group, an optionally substituted alkenyl group or an optionally substituted alkynyl group;    provided that X1 and X2 are not a hydrogen atom at the same time], as well as substances that act as antagonist against but not as agonist for the androgen receptor, pharmaceutically acceptable salts thereof, or prodrugs of the substances or their salts are useful as antiandrogenic agents and may be used as preventives or therapeutics of a disease selected from prostate cancer, prostatomegaly, male pattern alopecia, sexual prematurity, acne vulgaris, seborrhea and hursutism.

  通式(I)代表的化合物、其药学上可接受的盐，或化合物或其盐的原药： [其中 X1 和 X2 独立地代表氢原子或通式（II）所代表的基团 -Ar-A-R1 (II) Ra 代表氢原子或羟基的保护基团，Rb 和 Rc 与它们所结合的位于 3 位的碳原子结合在一起时，代表任选保护的-(C=O)-，虚线与实线结合代表形成单键或双键； 此外，Ar 代表单键或芳香烃基，A 代表亚甲基或-O-，R1 代表任选取代的烷基、任选取代的烯基或任选取代的炔基； 条件是 X1 和 X2 不是同时为氢原子]，以及可作为雄激素受体拮抗剂但不作为雄激素受体激动剂的物质、其药学上可接受的盐、或这些物质或其盐的原药可作为抗雄激素制剂，并可用作选自前列腺癌、前列腺肥大、男性型脱发、性早熟、寻常痤疮、脂溢性脱发和胡须增多症的疾病的预防或治疗剂。