(4AS,4BS,6AS,7S,9AS,9BS,11AR)-3-氟-1,4A,6A-三甲基-2- | 606101-78-4

• 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
• 中文名称: (4AS,4BS,6AS,7S,9AS,9BS,11AR)-3-氟-1,4A,6A-三甲基-2-
• 英文名称: (5α,17β)-2-fluoro-3-oxo-4-methyl-4-azaandrost-1-ene-17-carboxylic acid methyl ester
• 英文别名: 2-Fluoro-4-methyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid methyl ester；Methyl (4aS,4bS,6aS,7S,9aS,9bS,11aR)-3-fluoro-1,4a,6a-trimethyl-2-oxo-2,4a,4b,5,6,6a,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-indeno[5,4-f]quinoline-7-carboxylate；methyl (1S,3aS,3bS,5aR,9aS,9bS,11aS)-8-fluoro-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,9b,10,11-decahydro-1H-indeno[5,4-f]quinoline-1-carboxylate
• CAS: 606101-78-4
• 化学式: C₂₁H₃₀FNO₃
• 分子量: 363.473
• InChiKey: QBICUTLRKTYKCH-ADWQCJSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4AS,4BS,6AS,7S,9AS,9BS,11AR)-3-氟-1,4A,6A-三甲基-2- 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 N-甲基吗啉 、 lithium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 溴 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 甲醇 、 DMF (N,N-dimethyl-formamide) 、 水 为溶剂， 反应 18.0h， 生成 N-[1(R)-(3H-imidazo[4,5-b]-(5-bromopyridin)-2-yl)ethyl]-2-fluoro-4-methyl-3-oxo-4-aza-5α-androst-1-en-17β-carboxamide
  参考文献：
  名称：

  [EN] FLUORINATED 4-AZASTEROIDS AS ANDROGEN RECEPTOR MODULATORS
  [FR] 4-AZASTEROIDES FLUORES UTILISES EN TANT QUE MODULATEURS DU RECEPTEUR ANDROGENE

  摘要：

  结构式I的化合物以组织选择性方式调节雄激素受体（AR）。这些化合物可用于增强肌肉张力减弱和治疗由雄激素缺乏引起的或可以通过雄激素治疗改善的疾病，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、牙周疾病、骨折、骨重建手术后的骨损伤、肌少症、脆弱、老化皮肤、男性性激素缺乏症、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、炎性关节炎和关节修复、HIV消耗症、前列腺癌、良性前列腺增生（BPH）、癌症消耗症、阿尔茨海默病、肌肉营养不良、认知功能下降、性功能障碍、睡眠呼吸暂停、抑郁症、早发卵巢功能衰竭和自身免疫疾病，单独或与其他活性剂联合使用。

  公开号：

  WO2005105091A1
• 作为产物：
  描述：

  4-氮杂-5alpha-雄甾-1-烯-3-酮-17beta-羧酸甲酯 在 sodium hydride 、 N-氟代双苯磺酰胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 18.41h， 生成 (4AS,4BS,6AS,7S,9AS,9BS,11AR)-3-氟-1,4A,6A-三甲基-2-
  参考文献：
  名称：

  [EN] FLUORINATED 4-AZASTEROIDS AS ANDROGEN RECEPTOR MODULATORS
  [FR] 4-AZASTEROIDES FLUORES UTILISES EN TANT QUE MODULATEURS DU RECEPTEUR ANDROGENE

  摘要：

  结构式I的化合物以组织选择性方式调节雄激素受体（AR）。这些化合物可用于增强肌肉张力减弱和治疗由雄激素缺乏引起的或可以通过雄激素治疗改善的疾病，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、牙周疾病、骨折、骨重建手术后的骨损伤、肌少症、脆弱、老化皮肤、男性性激素缺乏症、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、炎性关节炎和关节修复、HIV消耗症、前列腺癌、良性前列腺增生（BPH）、癌症消耗症、阿尔茨海默病、肌肉营养不良、认知功能下降、性功能障碍、睡眠呼吸暂停、抑郁症、早发卵巢功能衰竭和自身免疫疾病，单独或与其他活性剂联合使用。

  公开号：

  WO2005105091A1

文献信息

• Process for making fluorinated 4-azasteroid derivatives
  申请人：Tan Lushi

  公开号：US20060252937A1

  公开（公告）日：2006-11-09

  The present invention relates to synthetic processes useful in the preparation of fluorinated 4-azasteroid derivatives that modulate androgen receptors and have application in the treatment of conditions caused by androgen deficiency or androgen receptor hyperactivity, such as osteoporosis, periodontal disease, bone fracture, frailty, erectile dysfunction, loss of libido, androgen-dependent cancers and sarcopenia. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.

  本发明涉及用于制备调节雄激素受体的氟化4-氮杂类固醇衍生物的合成过程，该衍生物在治疗由雄激素缺乏或雄激素受体过度活跃引起的疾病中具有应用，如骨质疏松症、牙周病、骨折、虚弱、勃起功能障碍、性欲丧失、依赖雄激素的癌症和肌少症。本发明还涵盖了在所披露的合成过程中有用的中间体及其制备方法。
• Salt of an androgen receptor modulator
  申请人：Lee Claire H.

  公开号：US20090048283A1

  公开（公告）日：2009-02-19

  The biphthalate salts of compound 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.

  化合物I的邻苯二甲酸盐以组织选择性方式调节雄激素受体（AR）。这些化合物可用于增强肌肉松弛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，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、牙周疾病、骨折、骨重建手术后的骨损伤、肌肉消耗症、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、艾滋病消耗症、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、肌肉营养不良、认知衰退、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，可单独使用或与其他活性剂结合使用。
• Polymorphs of an androgen receptor modulator
  申请人：Tan Lushi

  公开号：US20070129548A1

  公开（公告）日：2007-06-07

  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减弱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、艾滋病性消耗症、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、肌肉营养不良、认知下降、性功能障碍、睡眠呼吸暂停、抑郁症、早发性卵巢功能衰竭和自身免疫疾病，单独或与其他活性剂结合使用。
• [EN] 17-HETEROCYCLIC-4-AZASTEROID DERIVATIVES AS ANDROGEN RECEPTOR MODULATORS<br/>[FR] DERIVES DE 4-AZASTEROIDE 17-HETEROCYCLIQUES SERVANT DE MODULATEURS DU RECEPTEUR D'ANDROGENE
  申请人：MERCK & CO INC

  公开号：WO2005025579A1

  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的化合物是睾酮受体（AR）的调节剂，具有组织选择性。这些化合物在增强虚弱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、肌肉萎缩、衰弱、老化皮肤、男性睾丸功能减退症、女性更年期症状、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、艾滋病消瘦、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、癌症消耗症、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、早发卵巢功能衰竭和自身免疫疾病等方面具有作用，可以单独或与其他活性剂结合使用。
• [EN] FLUORINATED 4-AZASTEROID DERIVATIVES AS ANDROGEN RECEPTOR MODULATORS<br/>[FR] DERIVES DE 4-AZASTEROIDE FLUORE EN TANT QUE MODULATEUR DE RECEPTEUR ANDROGENIQUE
  申请人：MERCK & CO INC

  公开号：WO2003077919A1

  公开（公告）日：2003-09-25

  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 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, muscular dystrophies, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

  化合物I的结构式是雄激素受体（AR）的调节剂，具有组织选择性。它们在男性患者的前列腺或女性患者的子宫中作为雄激素受体拮抗剂，同时在骨骼和/或肌肉组织中作为雄激素受体激动剂，具有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的作用，包括骨质疏松症、骨质疏松、糖皮质激素诱导性骨质疏松症、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、动脉粥样硬化、高胆固醇血症、高脂血症、肥胖症、再生障碍性贫血和其他造血系统疾病、炎性关节炎和关节修复、艾滋病消耗综合征、前列腺癌、癌性消瘦、肌肉萎缩症、卵巢早衰和自身免疫性疾病，可单独使用或与其他活性剂联合使用。