3β-hydroxy-17-(5-pyrimidyl)androsta-5,16-diene | 428861-52-3

• 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: 3β-hydroxy-17-(5-pyrimidyl)androsta-5,16-diene
• 英文别名: 17-(5-pyrimidyl)androsta-5,16-dien-3β-ol；3β-hydroxy-17-(5-pyrimidyl)-androsta-5,16-diene；(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-pyrimidin-5-yl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-ol
• CAS: 428861-52-3
• 化学式: C₂₃H₃₀N₂O
• 分子量: 350.504
• InChiKey: XMXLTCQVKKQCBG-RFOVXIPZSA-N

物化性质

• 熔点：
  240-242 °C
• 沸点：
  506.8±50.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  46
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3β-hydroxy-17-(5-pyrimidyl)androsta-5,16-diene 在 环己酮 、 aluminum isopropoxide 作用下， 生成 17-(5-pyrimidyl)androsta-4,16-dien-3-one
  参考文献：
  名称：

  Novel steroidal pyrimidyl inhibitors of P450 17 (17α-hydroxylase/C17-20-lyase)

  摘要：

  DOI：

  10.1002/1521-4184(200112)334:12<373::aid-ardp373>3.0.co;2-x
• 作为产物：
  描述：

  醋酸去氢表雄酮 在 bis-triphenylphosphine-palladium(II) chloride sodium hydroxide 、 2,6-二叔丁基-4-甲基吡啶 、 sodium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 3β-hydroxy-17-(5-pyrimidyl)androsta-5,16-diene
  参考文献：
  名称：

  Novel steroidal pyrimidyl inhibitors of P450 17 (17α-hydroxylase/C17-20-lyase)

  摘要：

  DOI：

  10.1002/1521-4184(200112)334:12<373::aid-ardp373>3.0.co;2-x

文献信息

• Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens:  Synthesis, in Vitro Biological Activity, Pharmacokinetics, and Antitumor Activity in the LAPC4 Human Prostate Cancer Xenograft Model
  作者：Venkatesh D. Handratta、Tadas S. Vasaitis、Vincent C. O. Njar、Lalji K. Gediya、Ritesh Kataria、Pankaj Chopra、Donnell Newman、Rena Farquhar、Zhiyong Guo、Yun Qiu、Angela M. H. Brodie

  DOI：10.1021/jm040202w

  日期：2005.4.1

  were rationally designed and synthesized. The key reaction for synthesis of the benzoazoles involved the nucleophilic vinylic "addition-elimination" substitution reaction of 3beta-acetoxy-17-chloro-16-formylandrosta-5,16-diene (2) and benzoazole nucleophiles, while that for synthesis of pyrazines involved palladium-catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3beta-ol (13) with tributylstannyl

  合理设计和合成了新的化学实体，甾类C-17苯并唑（5、6、9和10）和吡嗪（14和15）。合成苯并恶唑的关键反应涉及亲核性乙烯基“加成消除”取代反应，该反应包括3β-乙酰氧基-17-氯-16-甲醛基-5,16-二烯（2）和苯并恶唑亲核反应，而吡嗪的合成反应涉及钯催化的17-碘-雄甾烯5,16-dien-3beta-ol（13）与三丁基锡烷基二嗪的交叉偶联反应。已显示某些化合物是人CYP17酶的有效抑制剂，以及野生型和突变雄激素受体（AR）的有效拮抗剂。最有效的CYP17抑制剂是3beta-hydroxy-17-（1H-benzimidazole-1-yl）androsta-5,16-diene（5，代号VN / 124-1），3beta-hydroxy-17-（5（1 ）-嘧啶基）androsta-5，16-二烯（15）和17-（1H-苯并咪唑-1-基）androsta-4,16-dien
• [EN] NOVEL STEROIDAL CYP17 INHIBITORS/ANTIANDROGENS<br/>[FR] NOUVEAUX INHIBITEURS/ANTI-ANDROGÈNES CYP17 STÉROÏDIENS
  申请人：TOKAI PHARMACEUTICALS

  公开号：WO2010091303A1

  公开（公告）日：2010-08-12

  Steroidal C-17 nitrogen-containing heterocycles of Formula I:,wherein: the ABCD ring structure is the nucleus of a steroid, or an analog thereof,; X is a group capable of coordinating a heme group of CYP 17, and Y is an hydroxyl functionality, a suitable ester, or a prodrug group, for the treatment of urogenital and/or androgen-related cancers, such as castration-resistant prostate cancer. The invention provides methods of synthesizing new chemical entities and methods of using the same in treating urogenital and/or androgen-related cancers.

  具有Formula I的类固醇C-17含氮杂环，其中：ABCD环结构是类固醇的核心，或其类似物；X是能够与CYP 17的血红素基团配位的基团，Y是一个羟基官能团、适当的酯或一种前药基团，用于治疗尿生殖器和/或与雄激素相关的癌症，如去势抵抗性前列腺癌。该发明提供了合成新化学实体的方法以及将其用于治疗尿生殖器和/或与雄激素相关癌症的方法。
• [EN] NOVEL PRODRUGS OF STEROIDAL CYP17 INHIBITORS/ANTIANDROGENS<br/>[FR] NOUVEAUX PROMÉDICAMENTS À BASE D'INHIBITEURS CYP17 STÉROÏDIENS/ANTI-ANDROGÈNES
  申请人：TOKAI PHARMACEUTICALS

  公开号：WO2010091306A1

  公开（公告）日：2010-08-12

  Prodrugs of C-17-heterocyclic- steroidal drugs providing improved oral bioavailability and phamacokinetics are described. The drugs are inhibitors of human CYP 17 enzyme, as well as potent antagonists of both wild type and mutant androgen receptors (AR), and are useful for the treatment of urogenital and/or androgen-related cancers, diseases and/or conditions, such as human prostate cancer, breast cancer, and prostate hyperplasia. The disclosure describes methods of synthesizing and using the prodrugs in cancer therapy.

  描述了C-17-杂环类固醇药物的前体，提供了改善口服生物利用度和药代动力学的结果。这些药物是人类CYP 17酶的抑制剂，同时也是野生型和突变雄激素受体（AR）的有效拮抗剂，适用于治疗泌尿生殖和/或与雄激素相关的癌症、疾病和/或病况，如人类前列腺癌、乳腺癌和前列腺增生。该披露描述了合成和使用这些前体在癌症治疗中的方法。
• Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens, In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity
  申请人：Brodie Angela

  公开号：US20100048912A1

  公开（公告）日：2010-02-25

  Described are steroidal C-17 benzoazoles, pyrimidinoazoles (azabenzoazoles) and diazines. Methods for their synthesis are also described, which include methods having a step of nucleophilic vinylic “addition-elimination” substitution reaction of 3β-acetoxy-17-chloro-16-formylandrosta-5,16-diene or analogs thereof and benzoazole or pyrimidinoazole nucleophiles and methods having a palladium catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3β-ol or analogs thereof with tributylstannyl diazines. The compounds are potent inhibitors of human CYP17 enzyme as well as potent antagonists of both wild type and mutant androgen receptors (AR). The compounds are useful for the treatment of human prostate cancer.

  描述了类固醇C-17苯并咪唑、嘧啶并咪唑（氮杂苯并咪唑）和二氮杂苯。还描述了它们的合成方法，包括具有3β-乙酰氧基-17-氯-16-甲酰基雄甾-5,16-二烯或其类似物和苯并咪唑或嘧啶并咪唑亲核试剂的亲核乙烯基“加成-消除”取代反应的方法，以及具有钯催化的17-碘雄甾-5,16-二烯-3β-醇或其类似物与三丁基锡二氮杂苯的交叉偶联反应的方法。这些化合物是人类CYP17酶的有效抑制剂，同时也是野生型和突变雄激素受体（AR）的有效拮抗剂。这些化合物可用于治疗人类前列腺癌。
• Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens;Synthesis In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity
  申请人：Brodie Angela

  公开号：US20100048913A1

  公开（公告）日：2010-02-25

  Described are steroidal C-17 benzoazoles, pyrimidinoazoles (azabenzoazoles) and diazines. Methods for their synthesis are also described, which include methods having a step of nucleophilic vinylic “addition-elimination” substitution reaction of 3β-acetoxy-17-chloro-16-formylandrosta-5,16-diene or analogs thereof and benzoazole or pyrimidinoazole nucleophiles and methods having a palladium catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3β-ol or analogs thereof with tributylstannyl diazines. The compounds are potent inhibitors of human CYP17 enzyme as well as potent antagonists of both wild type and mutant androgen receptors (AR). The compounds are useful for the treatment of human prostate cancer.

  描述了类固醇C-17苯并咪唑、嘧啶并咪唑（氮杂苯并咪唑）和二氮杂芳烃。还描述了它们的合成方法，其中包括将3β-乙酰氧基-17-氯-16-酰基雄甾-5,16-二烯或其类似物与苯并咪唑或嘧啶并咪唑亲核试剂进行亲核乙烯基“加成-消除”取代反应的方法以及将17-碘雄甾-5,16-二烯-3β-醇或其类似物与三丁基锡基二氮杂芳烃进行钯催化交叉偶联反应的方法。这些化合物是人类CYP17酶的有效抑制剂，同时也是野生型和突变雄激素受体（AR）的有效拮抗剂。这些化合物可用于治疗人类前列腺癌。