4-methyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid | 96692-02-3

• 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: 4-methyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid
• 英文别名: 4-methyl-4-aza-5α-androst-1-en-3-one 17β-carboxylic acid；3-Oxo-4-methyl-4-aza-5α-androst-1-ene-17β-carboxylic acid；(1S,3aS,3bS,5aR,9aR,9bS,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,9b,10,11-decahydro-1H-indeno[5,4-f]quinoline-1-carboxylic acid
• CAS: 96692-02-3
• 化学式: C₂₀H₂₉NO₃
• 分子量: 331.455
• InChiKey: ULXDYQMXHDINSW-ALHYADCGSA-N

物化性质

• 沸点：
  516.1±50.0 °C(Predicted)
• 密度：
  1.153±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 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：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-methyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid 以83%的产率得到N-(diphenylmethyl)-4-methyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide
  参考文献：
  名称：

  Azasteroid compounds for the treatment of prostatic hypertrophy, their

  摘要：

  式(I)的化合物：##STR1##（其中：R.sup.1是氢原子、未取代的烷基基团、芳基取代的烷基基团或杂环取代的烷基基团；R.sup.2是芳基取代的烷基基团、杂环取代的烷基基团或二芳胺基团；R.sup.3是氢原子、未取代的烷基基团、芳基取代的烷基基团或具有3至6个碳原子的烯基基团；以及由.alpha.-.beta.和.gamma.-.delta.表示的键中的每一个是碳-碳单键或碳-碳双键；）及其药学上可接受的盐和酯对于前列腺肥大的治疗和预防是有用的。我们还提供它们的制备方法。

  公开号：

  US05302621A1
• 作为产物：
  描述：

  甲基(4aR,4bS,6aS,7S,9aS,9bS,11aR)-1,4a,6a-三甲基-2-羰基-2,4a,4b,5,6,6a,7,8,9,9a,9b,10,11,11a-十四氢-1H-茚并[5,4-f]喹啉-7-羧酸酯 在 氢氧化钾 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 4-methyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid
  参考文献：
  名称：

  Azasteroid compounds for the treatment of prostatic hypertrophy, their

  摘要：

  式(I)的化合物：##STR1##（其中：R.sup.1是氢原子、未取代的烷基基团、芳基取代的烷基基团或杂环取代的烷基基团；R.sup.2是芳基取代的烷基基团、杂环取代的烷基基团或二芳胺基团；R.sup.3是氢原子、未取代的烷基基团、芳基取代的烷基基团或具有3至6个碳原子的烯基基团；以及由.alpha.-.beta.和.gamma.-.delta.表示的键中的每一个是碳-碳单键或碳-碳双键；）及其药学上可接受的盐和酯对于前列腺肥大的治疗和预防是有用的。我们还提供它们的制备方法。

  公开号：

  US05302621A1

文献信息

• [EN] 17-HETEROCYCLIC-4-AZASTEROID DERIVATIVES AS ANDROGEN RECEPTOR MODULATORS<br/>[FR] UTILISATION DE DERIVES 17-HETEROCYCLIQUES-4-AZASTEROIDIENS COMME MODULATEURS DU RECEPTEUR DES ANDROGENES
  申请人：MERCK & CO INC

  公开号：WO2005025572A1

  公开（公告）日：2005-03-24

  Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer’s disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

  结构式I的化合物以组织选择性方式调节雄激素受体（AR）。这些化合物在增强肌肉张力和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方面非常有用，包括骨质疏松症、骨质疏松症、糖皮质激素诱导的骨质疏松症、牙周病、骨折、骨重建手术后的骨损伤、肌少症、衰弱、老化皮肤、男性性腺功能减退、女性绝经后症状、动脉粥样硬化、高胆固醇血症、高脂血症、肥胖、再生障碍性贫血和其他造血系统疾病、炎症性关节炎和关节修复、艾滋病消耗综合征、前列腺癌、良性前列腺增生（BPH）、腹部脂肪过多、代谢综合征、2型糖尿病、癌症恶病质、阿尔茨海默病、肌肉萎缩症、认知下降、性功能障碍、睡眠呼吸暂停、抑郁症、卵巢功能早衰和自身免疫疾病等疾病的治疗，可以单独使用或与其他活性药物联合使用。
• 17.beta.-substituted Aza-androstane derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US05304562A1

  公开（公告）日：1994-04-19

  Compounds of the formula ##STR1## wherein carbon atoms 1 and 2 are linked by a single bond or a double bond, R.sub.1 is hydrogen, methyl or ethyl, and A is a group of the formula --N(--R.sub.2)--X-- wherein R.sub.2 is hydrogen or C.sub.1 -C.sub.4 alkyl and X is C.sub.1 -C.sub.12 alkylene or C.sub.3 -C.sub.6 cycloalkylidene; a group of the formula --N(--R.sub.2)--Y--Phe-- wherein R.sub.2 is as defined above, Y is a direct bond or C.sub.1 -C.sub.6 -alkylene and Phe is an unsubstituted or substituted phenylene radical; a group of the formula --O--X-- wherein X is as defined above, or a group --O--Y--Phe-- wherein Y and Phe are as defined above, are inhibitors of 5.alpha.-reductase and can be used for the therapeutic treatment of the human and animal body.

  式##STR1##中的化合物，其中碳原子1和2通过单键或双键连接，R.sub.1是氢、甲基或乙基，A是式--N(--R.sub.2)--X--的基团，其中R.sub.2是氢或C.sub.1 -C.sub.4烷基，X是C.sub.1 -C.sub.12烷基或C.sub.3 -C.sub.6环烷基亚甲基；式--N(--R.sub.2)--Y--Phe--的基团，其中R.sub.2如上定义，Y是直接键或C.sub.1 -C.sub.6-烷基亚甲基，Phe是未取代或取代的苯基基团；式--O--X--的基团，其中X如上定义，或基团--O--Y--Phe--，其中Y和Phe如上定义，是5α-还原酶的抑制剂，可用于治疗人体和动物体。
• Azasteroids: structure-activity relationships for inhibition of 5.alpha.-reductase and of androgen receptor binding
  作者：Gary H. Rasmusson、Glenn F. Reynolds、Nathan G. Steinberg、Edward Walton、Gool F. Patel、Tehming Liang、Margaret A. Cascieri、Anne H. Cheung、Jerry R. Brooks、Charles Berman

  DOI：10.1021/jm00161a028

  日期：1986.11

  In addition, 4-azasteroids with a D-homo ring or methyl substitution at C-7 (alpha and beta) or C-16 (alpha and beta) were prepared. The majority of the C-17 substituents were prepared from reactive intermediates derived from the 17 beta-COOH. Enhanced 5 alpha-reductase inhibition in both the human and rat enzyme assays is seen with 4-CN substitution on 3-oxo-delta 4 steroids and with a C-17 side

  制备了一系列类固醇，主要是4-氮杂类固醇，并在体外进行了测试，以作为人和大鼠前列腺5α-还原酶以及二氢睾丸激素与大鼠雄激素受体结合的抑制剂。主要的结构修饰是类固醇核的C-17位置的A环和连接部分的变化。新的A环修改包括碳环系列中的4-cyano-3-oxo-delta 4系统和1 alpha-CN，1 alpha-CH3、1 alpha，2 alpha-CH2、2 beta-F，2-aza， 3-oxo-4-aza系列中的2-oxa和A-homo变化。另外，制备了在C-7（α和β）或C-16（α和β）具有D-高环或甲基取代的4-氮杂甾类。大多数C-17取代基是由衍生自17β-COOH的反应性中间体制备的。在人和大鼠酶试验中，通过在3-oxo-delta 4类固醇上进行4-CN取代和在4-aza-3上结合了亲脂性取代的半极性基团的C-17侧链，可以看到增强的5α-还原酶抑制作用-oxo-5α
• 21-Heterocyclic-4-azasteroid derivatives as androgen receptor modulators
  申请人：Dankulich P. William

  公开号：US20070088047A1

  公开（公告）日：2007-04-19

  Compounds of structural formula (I) are modulators of the androgen receptor (AR) in a tissue selective manner. They are useful as agonists of the androgen receptor in bone and/or muscle tissue while antagonizing the AR in the prostate of a male patient or in the uterus of a female patient. These compounds are therefore useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive impairment, decreased libido, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

  结构式（I）的化合物以组织选择性方式调节雄激素受体（AR）。它们可作为雄激素受体在骨骼和/或肌肉组织中的激动剂，同时在男性患者的前列腺或女性患者的子宫中对抗雄激素受体。因此，这些化合物在增强肌肉张力和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方面具有用途，包括骨质疏松症、骨质疏松症、糖皮质激素诱导的骨质疏松症、牙周病、骨折、骨重建手术后的骨损伤、肌肉减少症、虚弱、老化皮肤、男性睾丸功能减退、女性绝经后症状、动脉粥样硬化、高胆固醇血症、高脂血症、肥胖、再生障碍性贫血和其他造血系统疾病、炎症性关节炎和关节修复、艾滋病消耗综合征、前列腺癌、癌症消耗综合征、阿尔茨海默病、肌肉萎缩症、认知障碍、性欲减退、卵巢早衰和自身免疫疾病等疾病的治疗，可单独使用或与其他活性药物联合使用。
• Androgen receptor modulators and methods for use thereof
  申请人：——

  公开号：US20030065004A1

  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 the androgen receptor in a tissue selective manner in a patient in need of such modulation, as well as in a method of agonizing the androgen receptor in a patient, and in particular the method wherein the androgen receptor is antagonized in the prostate of a male patient or in the uterus of a female patient and agonized 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, post-menopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, aplastic anemia and other hematopoietic disorders, pancreatic cancer, renal cancer, arthritis and joint repair, alone or in combination with other active agents. In addition, these compounds are useful as pharmaceutical composition ingredients alone and 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需要这种调节的患者中以组织选择性方式调节雄激素受体的方法中有用，以及在患者中激动雄激素受体的方法中有用，特别是在男性患者的前列腺或女性患者的子宫中拮抗雄激素受体并在骨骼和/或肌肉组织中激动雄激素受体的方法中有用。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、女性绝经后症状、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障碍、胰腺癌、肾癌、关节炎和关节修复，单独或与其他活性剂联合使用。此外，这些化合物作为药物组成部分单独或与其他活性剂联合使用也是有用的。