androst-4-en-3-on-17β-yl isonicotinate

• 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: androst-4-en-3-on-17β-yl isonicotinate
• 英文别名: (8R,9S,10R,13S,14S,17S)-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl isonicotinate；isonicotinic acid 3-oxoandrost-4-en-17β-yl ester；[(8R,9S,10R,13S,14S,17S)-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl] pyridine-4-carboxylate
• 化学式: C₂₅H₃₁NO₃
• 分子量: 393.526
• InChiKey: DNYIWPVEIQFOTC-BKWLFHPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  56.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  androst-4-en-3-on-17β-yl isonicotinate 、 methyl-2-diazo-2-(2-((3-phenylprop-2-yn-1-yl)oxy)phenyl)acetate 在 copper(l) chloride 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以61%的产率得到(8R,9S,10R,13S,14S,17S)-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl 7-phenyl-6H-chromeno[3,4-b]indolizine-9-carboxylate
  参考文献：
  名称：

  铜催化的由炔烃连接的重氮乙酸盐和吡啶的正式[1 + 2 + 2]环化反应：可得到多环吲哚嗪。

  摘要：

  据报导，铜连接的炔烃系重氮化合物与吡啶的正式[1 + 2 + 2]环化反应，可在温和的反应条件下提供多环稠合的吲哚并嗪，可合成用于高产。该方法的特点是使用廉价的铜催化剂和易于获得的起始原料，广泛的底物通用性和操作简便性。值得注意的是，多种天然产物衍生物在当前条件下是相容的，这表明该方法用于选择性修饰和修饰类似生物分子或药物的巨大潜力。

  DOI：

  10.1039/d0ob00222d
• 作为产物：
  描述：

  异烟酸 在 4-二甲氨基吡啶 、 2,4,6-三氯苯甲酰氯 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 0.33h， 生成 androst-4-en-3-on-17β-yl isonicotinate
  参考文献：
  名称：

  (Arene)Cl2Ru(II) complexes with N-coordinated estrogen and androgen isonicotinates: Interaction with sex hormone binding globulin and anticancer activity

  摘要：

  (arene)二氯化二钌(II)复合物与N-配位的雄激素（6）和雌激素（9）的异烟酸酰胺衍生物已被制备，并测试了其对雌激素受体（ERα）和性激素结合球蛋白（SHBG）的亲和力以及在癌细胞中的细胞毒性。新的复合物均未明显结合ER，且其中大多数与SHBG的结合力亦弱于相应的无金属甾体（7）。在MTT实验中，2-取代雌酮的Ru(p-甲乙基环己二烯)复合物（9）对激素依赖性（MCF-7乳腺癌和KB-V1宫颈癌）及激素非依赖性（518A2黑色素瘤）细胞的毒性与金属无甾体相当甚至更高。在加入外源性SHBG至HU实验中，其对复合物9的细胞毒性有所降低，且对某些甾体（7）的降低明显，可能是通过屏蔽及减少胞内摄取的途径实现。在无SHBG的情况下，雌激素复合物9被518A2黑色素瘤细胞摄入，并以ICP-OES定量其DNA的钌化修饰。它们亦能钌化鲑鱼精子DNA，但在EMSA实验中未改变质粒DNA的拓扑结构。此外，2-乙氧雌酮的Ru(p-甲乙基环己二烯)复合物（9c）在划痕修复实验中被证实可显著降低518A2黑色素瘤细胞的迁移能力。（C）2010 Elsevier Inc. 保留所有权利。

  DOI：

  10.1016/j.steroids.2010.12.009

文献信息

• Androstanes as androgen receptor modulators
  申请人：——

  公开号：US20040235808A1

  公开（公告）日：2004-11-25

  Compounds of structural formula (I) as herein defined are disclosed as useful in a method for modulating a function of the androgen receptor in a tissue selective manner in a patient in need of such modulation, as well as in a method of activating the function of the androgen receptor in a patient, and in particular the method wherein the function of the androgen receptor is blocked in the prostate of a male patient or in the uterus of a female patient and activated in bone and/or muscle tissue. These compounds are useful in the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteopenia, osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, female sexual dysfunction, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, aplastic anemia and other hematopoietic disorders, pancreatic cancer, renal cancer, prostate cancer, inflammatory arthritis and joint repair, alone or in combination with other active agents.

  本文所定义的结构式（I）的化合物被披露为在患者中以组织选择性的方式调节雄激素受体功能的方法中有用，以及在患者中激活雄激素受体功能的方法，特别是在男性患者的前列腺或女性患者的子宫中阻止雄激素受体功能并在骨骼和/或肌肉组织中激活雄激素受体功能的方法。这些化合物在治疗由雄激素缺乏引起或可以通过雄激素治疗改善的疾病中有用，包括骨质疏松症、骨质疏松、牙周病、骨折、骨重建手术后的骨损伤、肌肉萎缩、虚弱、老化皮肤、男性性腺功能减退、女性性功能障碍、绝经后妇女的症状、动脉硬化、高胆固醇血症、高脂血症、再生障碍性贫血和其他造血系统疾病、胰腺癌、肾癌、前列腺癌、炎性关节炎和关节修复，单独或与其他活性药物联合使用。
• Synthesis of pyridine-carboxylate derivatives of hydroxysteroids for liquid chromatography–electrospray ionization-mass spectrometry
  作者：Kouwa Yamashita、Sayuri Kobayashi、Satoshi Tsukamoto、Mitsuteru Numazawa

  DOI：10.1016/j.steroids.2006.10.005

  日期：2007.1

  Synthesis and liquid chromatography-electrospray ionization-mass spectrometric (LC-ESI-MS) behaviors of the picolinoyl, 6-methylpicolinoyl, nicotinoyl, 2-methoxynicotinoyl and isonicotinoyl derivatives of the hydroxysteroids estrone, estradiol, 3 beta-hydroxyandrost-5en-17-one (dehydroepiandrosterone) and testosterone in positive mode were investigated. Each steroid was converted to the corresponding pyridine-carboxylate derivative by the acyl chloride method or the mixed anhydride method using the corresponding free acids and 2-methyl-6-nitrobenzoic anhydride; in each case, the latter method principally gave a better yield. The pyridine-carboxylate derivative of each steroid exhibited a clear single peak in liquid chromatography with a reversed phase column and CH3CN-0.1% CH3COOH as a mobile phase. The positive-ESI-mass spectra of the picolinoyl, 6-methylpicolinoyl and 2-methoxynicotinoyl derivatives showed a predominance of [M+H](+), whereas [M+H+CH3CN](+) was observed with high intensity in the nicotinoyl and isonicotinoyl derivatives. Even in the case of estradiol, with its two hydroxyl groups, a single charged ion of [M+H](+) or [M+H+CH3CN](+) was observed in the positive-ESI-mass spectrum of each derivative. The results revealed that picolinoyl derivatization is a simple and versatile method suitable for the sensitive and specific determination of hydroxysteroids by LC-ESI-MS (selected reaction monitoring). (c) 2006 Elsevier Inc. All rights reserved.
• ANDROSTANES AS ANDROGEN RECEPTOR MODULATORS
  申请人：Merck & Co., Inc.

  公开号：EP1429779A2

  公开（公告）日：2004-06-23
• [EN] ANDROSTANES AS ANDROGEN RECEPTOR MODULATORS<br/>[FR] ANDROSTANES TENANT LIEU DE MODULATEURS DE RECEPTEUR D'ANDROGENE
  申请人：MERCK & CO INC

  公开号：WO2003026568A2

  公开（公告）日：2003-04-03

  Compounds of structural formula (I) as herein defined are disclosed as useful in a method for modulating a function of the androgen receptor in a tissue selective manner in a patient in need of such modulation, as well as in a method of activating the function of the androgen receptor in a patient, and in particular the method wherein the function of the androgen receptor is blocked in the prostate of a male patient or in the uterus of a female patient and activated in bone and/or muscle tissue. These compounds are useful in the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteopenia, osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, female sexual dysfunction, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, aplastic anemia and other hematopoietic disorders, pancreatic cancer, renal cancer, prostate cancer, inflammatory arthritis and joint repair, alone or in combination with other active agents.