2,2,4-trimethyl-1,2-dihydro-6-oxa-1-azachrysen-5-one | 179894-93-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 2,2,4-trimethyl-1,2-dihydro-6-oxa-1-azachrysen-5-one
• 英文别名: 2,2,4-trimethyl-1H-chromeno[3,4-f]quinolin-5-one
• CAS: 179894-93-0
• 化学式: C₁₉H₁₇NO₂
• 分子量: 291.349
• InChiKey: PHIFGUAYVILRHC-UHFFFAOYSA-N

物化性质

• 熔点：
  190-191 °C
• 沸点：
  486.2±45.0 °C(Predicted)
• 密度：
  1.183±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2,4-trimethyl-1,2-dihydro-6-oxa-1-azachrysen-5-one 在 二异丁基氢化铝 、 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 生成 5-Methoxy-2,2,4-trimethyl-2,5-dihydro-1H-6-oxa-1-aza-chrysene
  参考文献：
  名称：

  5-Alkyl 1,2-dihydrochromeno[3,4-f]quinolines: a novel class of nonsteroidal progesterone receptor modulators

  摘要：

  A series of nonsteroidal human progesterone receptor (hPR) agonists, 5-alkyl 1,2-dihydrochromeno[3,4-f]quinolines, was synthesized and evaluated in cotransfection and competitive receptor binding assays. The 5-alkyl substitution was shown to be responsible for the agonist activity and substitution at C9 dramatically enhanced the potency. A number of analogues in this series showed activities similar to or better than progesterone in the cotransfection and binding assays and analogue 15 exhibited similar in vivo activity as medroxyprogesterone acetate (MPA) in murine uterine wet weight/mammary gland morphology assays. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00608-8
• 作为产物：
  描述：

  8-nitro-6H-benzo[c]chromen-6-one 在 palladium on activated charcoal 氢气 、 碘 作用下， 以 乙酸乙酯 为溶剂， 反应 48.0h， 生成 2,2,4-trimethyl-1,2-dihydro-6-oxa-1-azachrysen-5-one
  参考文献：
  名称：

  5-芳基-1,2-二氢色素[3,4-f]喹啉：一类新的非甾体类人孕激素受体激动剂。

  摘要：

  描述了新型非甾体类人孕激素受体（hPR）激动剂5-芳基-1,2-二氢-5H-chromeno [3,4-f]喹啉2的开发。将5-芳基基团引入1,2-二氢香豆素[3,4-f]喹啉核心1是促孕活动的关键。对5-芳基取代基的结构活性关系（SAR）研究产生了一系列有效的hPR激动剂，它们在细胞内显示出与天然激素孕酮（EC50 = 2.9 nM）类似的生物学活性（EC50 = 8-30 nM）。效率范围从28％到96％的检测。大多数类似物表现出与孕酮（Ki = 3.5 nM）相似或更高的结合亲和力（Ki = 0.41-3.6 nM）。三个代表性的类似物（13、15和24）在去卵巢大鼠的乳腺形态/子宫湿重测定中显示了体内活性。

  DOI：

  10.1021/jm9705768

文献信息

• NOVEL 1,2-DIHYDROQUINOLINE DERIVATIVE HAVING (SUBSTITUTED PHENYL OR SUBSTITUTED HETEROCYCLIC) CARBONYLOXY LOWER ALKYL GROUP AND ESTER-INTRODUCED PHENYL GROUP AS SUBSTITUENTS
  申请人：Matsuda Mamoru

  公开号：US20090298826A1

  公开（公告）日：2009-12-03

  The compounds represented in general formula (1) and a salt thereof are useful for glucocorticoid receptor modulator. The R 1 represents a hydrogen atom or a lower alkyl group; R 2 represents a hydrogen atom or a lower alkyl group; R 3 and R 4 may be the same or different and represent a hydrogen atom or a lower alkyl group; R 5 represents a hydrogen atom or a lower alkyl group; R 6 represents a halogen atom, a lower alkyl group, a hydroxy group, a lower alkoxy group, a nitro group or a cyano group; X represents —C(O)—, —C(O)NR 8 —, —S(O) 2 — and the like; R 7 and/or R 8 may be the same or different and represent a hydrogen atom, a lower alkyl group which may have a substituent, an aryl group which may have a substituent, a heterocyclic group which may have a substituent, a lower alkoxy group which may have a substituent and the like; Y represents a lower alkylene group; Z represents a benzene ring or a heterocyclic ring; and P represents 0, 1, 2 or 3.

  通用公式（1）中代表的化合物及其盐对糖皮质激素受体调节剂非常有用。其中，R1代表氢原子或较低的烷基基团；R2代表氢原子或较低的烷基基团；R3和R4可以相同也可以不同，代表氢原子或较低的烷基基团；R5代表氢原子或较低的烷基基团；R6代表卤素原子、较低的烷基基团、羟基、较低的烷氧基、硝基或氰基；X代表—C(O)—、—C(O)NR8—、—S(O)2—等；R7和/或R8可以相同也可以不同，代表氢原子、可能具有取代基团的较低烷基基团、可能具有取代基团的芳基、可能具有取代基团的杂环基团、可能具有取代基团的较低烷氧基团等；Y代表较低的烷基烯基团；Z代表苯环或杂环环；P代表0、1、2或3。
• 5-Aryl-1,2-dihydrochromeno[3,4-<i>f</i>]quinolines:  A Novel Class of Nonsteroidal Human Progesterone Receptor Agonists
  作者：Lin Zhi、Christopher M. Tegley、E. Adam Kallel、Keith B. Marschke、Dale E. Mais、Marco M. Gottardis、Todd K. Jones

  DOI：10.1021/jm9705768

  日期：1998.1.1

  The development of a novel class of nonsteroidal human progesterone receptor (hPR) agonists, 5-aryl-1,2-dihydro-5H-chromeno[3,4-f]quinolines 2, is described. The introduction of a 5-aryl group into the 1,2-dihydrocoumarino[3,4-f]quinoline core 1 is the key for progestational activities. The structure-activity relationship (SAR) studies of the 5-aryl substituents generated a series of potent hPR agonists

  描述了新型非甾体类人孕激素受体（hPR）激动剂5-芳基-1,2-二氢-5H-chromeno [3,4-f]喹啉2的开发。将5-芳基基团引入1,2-二氢香豆素[3,4-f]喹啉核心1是促孕活动的关键。对5-芳基取代基的结构活性关系（SAR）研究产生了一系列有效的hPR激动剂，它们在细胞内显示出与天然激素孕酮（EC50 = 2.9 nM）类似的生物学活性（EC50 = 8-30 nM）。效率范围从28％到96％的检测。大多数类似物表现出与孕酮（Ki = 3.5 nM）相似或更高的结合亲和力（Ki = 0.41-3.6 nM）。三个代表性的类似物（13、15和24）在去卵巢大鼠的乳腺形态/子宫湿重测定中显示了体内活性。
• Novel 1-2-Dihydroquinoline Derivative Having Glucocorticoid Receptor Binding Activity
  申请人：Matsuda Mamoru

  公开号：US20090326009A1

  公开（公告）日：2009-12-31

  An object of the present invention is to study synthesis of a novel 1,2-dihydroquinoline derivative and to find a pharmacological action of the derivative. A compound represented by the general formula (1) or a salt thereof is effective in the treatment of a glucocorticoid receptor-related disease. In the formula, the ring X represents a benzene ring or a pyridine ring; R 1 represents a halogen atom, an alkyl group, a hydroxy group, an alkoxy group, an amino group or the like; p represents an integer of 0 to 5; R 2 represents a halogen atom, an alkyl group, a hydroxy group or the like; q represents an integer of 0 to 2; R 3 represents a hydrogen atom, an alkyl group, an alkenyl group or the like; R 4 and R 5 represent a hydrogen atom or the like; R 6 represents a hydrogen atom or the like; A represents an alkylene group or the like; and R 7 represents OR 8 , NR 8 R 9 , SR 8 , S(O)R 8 or S(O) 2 R 8 , wherein R 8 represents an aryl group, a heterocyclic group or the like and R 9 represents a hydrogen atom or the like.

  本发明的目的是研究合成一种新型1,2-二氢喹啉衍生物，并发现该衍生物的药理作用。通式（1）表示的化合物或其盐在治疗糖皮质激素受体相关疾病方面具有有效性。在该式中，环X表示苯环或吡啶环；R1表示卤素原子、烷基、羟基、烷氧基、氨基或类似物；p表示0至5的整数；R2表示卤素原子、烷基、羟基或类似物；q表示0至2的整数；R3表示氢原子、烷基、烯基或类似物；R4和R5表示氢原子或类似物；R6表示氢原子或类似物；A表示烷基链或类似物；R7表示OR8、NR8R9、SR8、S（O）R8或S（O）2R8，其中R8表示芳基、杂环基或类似物，R9表示氢原子或类似物。
• Indoline derivatives
  申请人：Fensome Andrew

  公开号：US20070259944A1

  公开（公告）日：2007-11-08

  This invention relates to substituted indoline derivative compounds which are antagonists of the progesterone receptor, their preparation and pharmaceutical utility, particularly including contraception and treatment of benign or malignant neoplastic diseases, having the general structure: wherein R 1 and R 2 may be single substituents or fused to form spirocyclic rings.

  本发明涉及取代的吲哚啉衍生物化合物，其是孕激素受体拮抗剂，其制备和药用，特别包括避孕和治疗良性或恶性肿瘤疾病，具有以下一般结构：其中R1和R2可以是单个取代基或融合形成螺环。
• CYCLOTHIOCARBAMATE DERIVATIVES AS PROGESTERONE RECEPTOR MODULATORS
  申请人：Zhang Puwen

  公开号：US20090281096A1

  公开（公告）日：2009-11-12

  Methods of using compounds which are progesterone receptor agonists for contraception and the treatment of progesterone-related maladies alone or in combination with an estrogen receptor agonist or progesterone receptor antagonist are provided. These compounds have the structure: wherein R 1 , R 2 , R 3 , R 4 , R 5 , and Q 1 are defined herein.

  本发明提供了使用化合物作为孕激素受体激动剂进行避孕和治疗孕激素相关疾病的方法，这些化合物可以单独使用或与雌激素受体激动剂或孕激素受体拮抗剂联合使用。这些化合物具有以下结构：其中R1，R2，R3，R4，R5和Q1如本文所定义。