3-oxoandrost-4-ene-17β-carboxylic acid chloride | 57072-90-9

• 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: 3-oxoandrost-4-ene-17β-carboxylic acid chloride
• 英文别名: 3-oxo-androst-4-ene-17β-carbonyl chloride；3-Oxoandrost-4-ene-17beta-carbonyl chloride；(8S,9S,10R,13S,14S,17S)-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-17-carbonyl chloride
• CAS: 57072-90-9
• 化学式: C₂₀H₂₇ClO₂
• 分子量: 334.886
• InChiKey: LCXWGDKPBJOJDK-UDCWSGSHSA-N

物化性质

• 沸点：
  446.0±45.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-oxoandrost-4-ene-17β-carboxylic acid chloride 在 platinum on activated charcoal 吡啶 、 potassium permanganate 、 sodium periodate 、 氢气 、 sodium carbonate 作用下， 以 水 、 乙二醇 、 甲苯 、 叔丁醇 为溶剂， 40.0~180.0 ℃ 、303.98 kPa 条件下， 反应 12.08h， 生成 (1S,3aS,3bS,5aR,9aR,9bS,11aS)-6,9a,11a-trimethyl-N-[(2R)-4-methyl-1-(methylamino)-1-oxopentan-2-yl]-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinoline-1-carboxamide
  参考文献：
  名称：

  Substrate interaction with 5α-reductase enzyme: influence of the 17β-chain chirality in the mechanism of action of 4-azasteroid inhibitors

  摘要：

  A series of steroidal compounds were synthesized in order to evaluate the possible influence of the configuration of a stereocenter in the 17 beta -side chain on the inhibitory activity on the enzyme 5 alpha -reductase (5AR). For this purpose diastereomerically pure 4-azasteroids epimers at C-22 were prepared (compounds 1-11) and tested as inhibitors of 5AR in 'in vitro' tests, The obtained data showed that in most cases the couples of epimers possess a significant difference in their biological activity. We also considered, for the tested molecules, a series of chemico-physical parameters in order to find a possible correlation with their biological activity. The findings allowed us to propose a model of the binding site of 5AR which comprises also, for 4-azasteroid inhibitors, the configurational aspect of the 17 beta -side chain. (C) 2001 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(01)00114-3
• 作为产物：
  描述：

  去氧皮质酮 在 硫酸 、 高碘酸 作用下， 以 水 、 丙酮 、 苯 为溶剂， 反应 12.75h， 生成 3-oxoandrost-4-ene-17β-carboxylic acid chloride
  参考文献：
  名称：

  Microbial hydroxylation of steroids. 8. Incubation of Cn halo- and other substituted steroids with Cn hydroxylating fungi

  摘要：

  一系列C-21取代孕酮衍生物（R = F、Cl、Br、CH3）已经制备，并与C-21羟化真菌A. niger培养。观察到当R = Cl、Br或CH3时未发生生物转化，但当R = F时，在未知位置发生了少量羟基化。两种C-11β取代孕酮衍生物（R = F、OH）被C-11α羟化酶R. stolonifer转化为相应的C-11酮，但C-11β羟化酶（C. lunata）无法使用C-11α羟基底物进行类似转化。C. lunata在低产率下将C-11β氟底物羟化为C-14α和C-21。制备了C-7α和-7β-羟基雄烯-4-烯-3,17-二酮，并分别与C-7β羟化（R. stolonifer）和C-7α羟化（M. griseocyanus）真菌培养。未观察到酮形成。同样，C-6β羟化酶R. arrhizus无法转化C-6α-羟基底物或C-6α-或C-6β-羟基B-诺甾醇。未观察到任何底物的卤素氧化。11β-氟孕酮的¹³C–¹⁹F偶合常数表明氟与C-18和C-19之间存在空间相互作用。

  DOI：

  10.1139/v82-027

文献信息

• Iridium-Catalyzed Three-component Coupling Reaction of Carbon Dioxide, Amines, and Sulfoxonium Ylides
  作者：Huanfeng Jiang、Hao Zhang、Wenfang Xiong、Chaorong Qi、Wanqing Wu、Lu Wang、Ruixiang Cheng

  DOI：10.1021/acs.orglett.9b00072

  日期：2019.2.15

  The first iridium-catalyzed three-component coupling reaction of carbon dioxide, amines, and sulfoxonium ylides has been developed, providing an efficient and straightforward method for the construction of a range of structurally diverse O-β-oxoalkyl carbamates in moderate to excellent yields. This novel protocol features the use of readily available substrates, wide substrate scope, and good functional

  已经开发出第一催化铱，二氧化碳，胺和亚硫酸sulf鎓烷基化物的三组分偶联反应，提供了一种有效且直接的方法来以中等至优异的产率构建一系列结构多样的O -β-氧代烷基氨基甲酸酯。这种新颖的协议的特点是易于使用的底物，广泛的底物范围和良好的官能团耐受性。此外，无光气策略已成功应用于潜在的抗肿瘤药物的合成。
• [EN] PROCESS FOR THE PREPARATION OF 17ß-SUBSTITUTED-3-OXO-4-AZA-5ALPHA-ANDROSTANE DERIVATIVES<br/>[FR] PROCEDE DE PREPARATION DE DERIVES DE 17ss-SUBSTITUE-3-OXO-4-AZA-5ALPHA-ANDROSTANE
  申请人：RANBAXY LAB LTD

  公开号：WO2005075497A1

  公开（公告）日：2005-08-18

  Process for the preparation of 17ß-substituted-3-oxo-4-aza-5α-androstane derivatives, which are useful intermediates for the synthesis of 3-oxo-4-aza-5α-androst-1-ene derivatives including finasteride, is provided.

  提供了制备17ß-取代-3-氧代-4-氮杂-5α-雄烷衍生物的过程，这些衍生物是合成3-氧代-4-氮杂-5α-雄烷-1-烯衍生物（包括非那雄胺）有用的中间体。
• PROCESS FOR THE PREPARATION OF DUTASTERIDE
  申请人：Mallela Sambhu Prasad Sarma

  公开号：US20120157683A1

  公开（公告）日：2012-06-21

  The present invention provides an improved process for the preparation of Dutasteride (I) which comprises: (i) reacting 4-aza-5α-androst-1-en-3-one-17β-carboxylic acid (VII), Formula VII with sulfonic acid anhydride (RSO 2 ) 2 O in presence of base to produce an intermediate compound of Formula (XIII), wherein R represents C 1-6 alkyl, C 1-6 halo alkyl, C 6-10 aryl, halo aryl; (ii) condensing compound of Formula (XIII) with 2,5-bis(trifluoromethyl)aniline (III), Formula (III) in the presence or absence of a base to produce Dutasteride (I).

  本发明提供一种改进的Dutasteride（I）制备方法，其包括：（i）在碱存在下，将4-aza-5α-androst-1-en-3-one-17β-carboxylic acid（VII）（式VII）与磺酸酐（RSO2）2O反应，以产生中间化合物（XIII）（式XIII），其中R代表C1-6烷基，C1-6卤代烷基，C6-10芳基，卤代芳基；（ii）在存在或缺乏碱的情况下，将化合物（XIII）与2,5-双（三氟甲基）苯胺（III）（式III）缩合，以产生Dutasteride（I）。
• Androstane 17-beta-carboxamides as androgen receptor modulators
  申请人：——

  公开号：US20040220159A1

  公开（公告）日：2004-11-04

  Compounds of structural formula as herein defined are disclosed as useful in a method for modulating 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 osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, female sexual dysfunction, post-menopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, aplastic anemia and other hematopoietic disorders, pancreatic cancer, renal cancer, prostate cancer, arthritis and joint repair, alone or in combination with other active agents.

  本文所定义的结构式化合物被披露为在需要这种调节的患者中以组织选择性的方式调节雄激素受体的方法中有用，以及在患者中激活雄激素受体功能的方法中有用，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、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、关节炎和关节修复，可单独使用或与其他活性剂联合使用。
• Phenylsubstituted 4-azasteroid fluoroderivatives
  申请人：Pharmacia & Upjohn, S.p.A.

  公开号：US06114345A1

  公开（公告）日：2000-09-05

  Compounds of formula (I), wherein: the symbol ---- represents a single or a double bond; R is a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group; R.sub.f and R'.sub.f, each independently, are C.sub.1 -C.sub.4 alkyl groups substituted by one or more fluorine atoms; and R.sub.1 and R.sub.2, each independently, are selected from: a hydrogen atom; a phenyl group; a C.sub.1 -C.sub.4 alkyl group unsubstituted or substituted by one or more fluorine atoms; a halogen atom; a cyano (CN) group; a group OR.sub.4, wherein R.sub.4 is a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group; a group SR.sub.5, wherein R.sub.5 is a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group; and a group COR.sub.6, wherein R.sub.6 is a group OR.sub.4 in which R.sub.4 is as defined above or a C.sub.1 -C.sub.4 alkyl group unsubstituted or substituted by one or more fluorine atoms. They are useful as testosterone 5a-reductase inhibitors.

  式(I)的化合物，其中：符号----表示单键或双键；R是氢原子或C.sub.1-C.sub.4烷基基团；R.sub.f和R'.sub.f各自独立地是C.sub.1-C.sub.4烷基基团，被一个或多个氟原子取代；R.sub.1和R.sub.2各自独立地选择自：氢原子；苯基；未取代或被一个或多个氟原子取代的C.sub.1-C.sub.4烷基基团；卤素原子；氰基（CN）基团；OR.sub.4基团，其中R.sub.4是氢原子或C.sub.1-C.sub.4烷基基团；SR.sub.5基团，其中R.sub.5是氢原子或C.sub.1-C.sub.4烷基基团；以及COR.sub.6基团，其中R.sub.6是OR.sub.4基团，其中R.sub.4如上所定义，或未取代或被一个或多个氟原子取代的C.sub.1-C.sub.4烷基基团。它们可用作睾酮5α-还原酶抑制剂。