4,4-diethyl-6-nitro-1,4-dihydro-2H-3,1-benzoxazin-2-one | 850198-47-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4,4-diethyl-6-nitro-1,4-dihydro-2H-3,1-benzoxazin-2-one
• 英文别名: 4,4-diethyl-6-nitro-1H-3,1-benzoxazin-2-one
• CAS: 850198-47-9
• 化学式: C₁₂H₁₄N₂O₄
• 分子量: 250.254
• InChiKey: NJTBNOAOHCDIMB-UHFFFAOYSA-N

物化性质

• 沸点：
  330.6±42.0 °C(Predicted)
• 密度：
  1.219±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,4-diethyl-6-nitro-1,4-dihydro-2H-3,1-benzoxazin-2-one 在 palladium on activated charcoal sodium tetrahydroborate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 6-amino-4,4-diethyl-1-methyl-1,4-dihydro-2H-3,1-benzoxazin-2-one
  参考文献：
  名称：

  SAR studies of 6-(arylamino)-4,4-disubstituted-1-methyl-1,4-dihydro-benzo[d][1,3]oxazin-2-ones as progesterone receptor antagonists

  摘要：

  We previously disclosed that 6-aryl benzoxazin-2-ones were PR modulators. In a continuation of this work we examined the SAR of new 6-arylamino benzoxazinones and found the targets 1-25, with an extra amino linker between the pendent 6-aryl groups and benzoxazinone or benzoxazine-2-thione core, were PR antagonists. A series of compounds with substituents at the 1- and 4-positions as well as different 6-aryl groups were prepared and tested in the T47D cell alkaline phosphatase assay. Interestingly, the SAR unveiled from the 6-arylamino benzoxazinones was quite different from those of their parent compounds. For example, in contrast to the 6-aryl benzoxazinones, methyl substitution at the 1-position significantly increased the potency of 6-arylamino benzoxazinones. Several 6-arylamino benzoxazinones (e.g., 12, IC50 = 5.0 nM) had low nanomolar in vitro potency as PR antagonists in the T47D cell alkaline phosphatase assay. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.060
• 作为产物：
  描述：

  1-(2-氨基-苯基)-丙烷-1-酮 在 硫酸 、 亚硝酸 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 生成 4,4-diethyl-6-nitro-1,4-dihydro-2H-3,1-benzoxazin-2-one
  参考文献：
  名称：

  SAR studies of 6-(arylamino)-4,4-disubstituted-1-methyl-1,4-dihydro-benzo[d][1,3]oxazin-2-ones as progesterone receptor antagonists

  摘要：

  We previously disclosed that 6-aryl benzoxazin-2-ones were PR modulators. In a continuation of this work we examined the SAR of new 6-arylamino benzoxazinones and found the targets 1-25, with an extra amino linker between the pendent 6-aryl groups and benzoxazinone or benzoxazine-2-thione core, were PR antagonists. A series of compounds with substituents at the 1- and 4-positions as well as different 6-aryl groups were prepared and tested in the T47D cell alkaline phosphatase assay. Interestingly, the SAR unveiled from the 6-arylamino benzoxazinones was quite different from those of their parent compounds. For example, in contrast to the 6-aryl benzoxazinones, methyl substitution at the 1-position significantly increased the potency of 6-arylamino benzoxazinones. Several 6-arylamino benzoxazinones (e.g., 12, IC50 = 5.0 nM) had low nanomolar in vitro potency as PR antagonists in the T47D cell alkaline phosphatase assay. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.060

文献信息

• 6-Amino-1,4-dihydro-benzo[d][1,3] oxazin-2-ones and analogs useful as progesterone receptor modulators
  申请人：Zhang Puwen

  公开号：US20050085470A1

  公开（公告）日：2005-04-21

  Compounds having the structure of formula I are provided. In formula I, R 1 is H, OH, substituted or unsubstituted C 1 to C 3 alkyl, C 1 to C 3 perfluoroalkyl, or COR 6 ; R 6 is H, substituted or unsubstituted C 1 to C 4 alkyl, aryl, substituted or unsubstituted C 1 to C 4 alkoxy, substituted or unsubstituted C 1 to C 3 aminoalkyl; R 2 and R 3 are H, substituted or unsubstituted C 1 to C 6 alkyl, C 1 to C 6 perfluoroalkyl, substituted or unsubstituted C 2 to C 6 alkenyl, substituted or unsubstituted C 2 to C 6 alkynyl, substituted or unsubstituted C 3 to C 6 cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic; or R 2 and R 3 are fused to form spirocyclic rings; R 4 is NHR 7 , OR 7 , NHSO 2 R 7 , or OSO 2 R 7 ; Q is O, S, NR 8 , or CR 9 R 10 ; or a pharmaceutically acceptable salt, ester, or prodrug thereof. Such compounds are useful as progesterone receptor modulators and for treating progesterone receptor related conditions.

  提供具有公式I结构的化合物。在公式I中，R1为H，OH，取代或未取代的C1至C3烷基，C1至C3全氟烷基，或COR6；R6为H，取代或未取代的C1至C4烷基，芳基，取代或未取代的C1至C4甲氧基，取代或未取代的C1至C3氨基烷基；R2和R3为H，取代或未取代的C1至C6烷基，C1至C6全氟烷基，取代或未取代的C2至C6烯基，取代或未取代的C2至C6炔基，取代或未取代的C3至C6环烷基，取代或未取代的芳基，或取代或未取代的杂环；或者R2和R3融合形成螺环；R4为NHR7，OR7，NHSO2R7，或OSO2R7；Q为O，S，NR8，或CR9R10；或其药用可接受的盐，酯或前药。这些化合物可用作孕激素受体调节剂，并用于治疗与孕激素受体相关的疾病。
• 6-Amino-1,4-dihydro-benzo[d][1,3]oxazin-2-ones and analogs useful as progesterone receptor modulators
  申请人：Zhang Puwen

  公开号：US20070225281A1

  公开（公告）日：2007-09-27

  Compounds having the structure of formula I are provided. In formula I, R 1 is H, OH, substituted or unsubstituted C 1 to C 3 alkyl, C 1 to C 3 perfluoroalkyl, or COR 6 ; R 6 is H, substituted or unsubstituted C 1 to C 4 alkyl, aryl, substituted or unsubstituted C 1 to C 4 alkoxy, substituted or unsubstituted C 1 to C 3 aminoalkyl; R 2 and R 3 are H, substituted or unsubstituted C 1 to C 6 alkyl, C 1 to C 6 perfluoroalkyl, substituted or unsubstituted C 2 to C 6 alkenyl, substituted or unsubstituted C 2 to C 6 alkynyl, substituted or unsubstituted C 3 to C 6 cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic; or R 2 and R 3 are fused to form spirocyclic rings; R 4 is NHR 7 , OR 7 , NHSO 2 R 7 , or OSO 2 R 7 ; Q is O, S, NR 8 , or CR 9 R 10 ; or a pharmaceutically acceptable salt, ester, or prodrug thereof. Such compounds are useful as progesterone receptor modulators and for treating progesterone receptor related conditions.

  提供了具有式I结构的化合物。在式I中，R1是H、OH、取代或未取代的C1到C3烷基、C1到C3全氟烷基或COR6；R6是H、取代或未取代的C1到C4烷基、芳基、取代或未取代的C1到C4甲氧基、取代或未取代的C1到C3氨基烷基；R2和R3是H、取代或未取代的C1到C6烷基、C1到C6全氟烷基、取代或未取代的C2到C6烯基、取代或未取代的C2到C6炔基、取代或未取代的C3到C6环烷基、取代或未取代的芳基或取代或未取代的杂环基；或R2和R3融合形成螺环；R4是NHR7、OR7、NHSO2R7或OSO2R7；Q是O、S、NR8或CR9R10；或其药学上可接受的盐、酯或前药。这些化合物可用作孕激素受体调节剂，并用于治疗孕激素受体相关疾病。
• 6-amino-1,4-dihydro-benzo[d][1,3] oxazin-2-ones and analogs useful as progesterone receptor modulators
  申请人：Wyeth

  公开号：US07247625B2

  公开（公告）日：2007-07-24

  Compounds having the structure of formula I are provided. In formula I, R1 is H, OH, substituted or unsubstituted C1 to C3 alkyl, C1 to C3 perfluoroalkyl, or COR6; R6 is H, substituted or unsubstituted C1 to C4 alkyl, aryl, substituted or unsubstituted C1 to C4 alkoxy, substituted or unsubstituted C1 to C3 aminoalkyl; R2 and R3 are H, substituted or unsubstituted C1 to C6 alkyl, C1 to C6 perfluoroalkyl, substituted or unsubstituted C2 to C6 alkenyl, substituted or unsubstituted C2 to C6 alkynyl, substituted or unsubstituted C3 to C6 cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic; or R2 and R3 are fused to form spirocyclic rings; R4 is NHR7, OR7, NHSO2R7, or OSO2R7; Q is O, S, NR8, or CR9R10; or a pharmaceutically acceptable salt, ester, or prodrug thereof. Such compounds are useful as progesterone receptor modulators and for treating progesterone receptor related conditions.

  提供了具有公式I结构的化合物。在公式I中，R1是H，OH，取代或未取代的C1到C3烷基，C1到C3全氟烷基或COR6; R6是H，取代或未取代的C1到C4烷基，芳基，取代或未取代的C1到C4烷氧基，取代或未取代的C1到C3氨基烷基; R2和R3是H，取代或未取代的C1到C6烷基，C1到C6全氟烷基，取代或未取代的C2到C6烯基，取代或未取代的C2到C6炔基，取代或未取代的C3到C6环烷基，取代或未取代的芳基或取代或未取代的杂环基; 或R2和R3融合形成螺环; R4是NHR7，OR7，NHSO2R7或OSO2R7; Q是O，S，NR8或CR9R10; 或其药学上可接受的盐，酯或前药。这些化合物可用作孕激素受体调节剂，并用于治疗孕激素受体相关疾病。
• 6-amino-1,4-dihydro-benzo[d][1,3]oxazin-2-ones and analogs useful as progesterone receptor modulators
  申请人：Wyeth

  公开号：US07354915B2

  公开（公告）日：2008-04-08

  Compounds having the structure of formula I are provided. In formula I, R1 is H, OH, substituted or unsubstituted C1 to C3 alkyl, C1 to C3 perfluoroalkyl, or COR6; R6 is H, substituted or unsubstituted C1 to C4 alkyl, aryl, substituted or unsubstituted C1 to C4 alkoxy, substituted or unsubstituted C1 to C3 aminoalkyl; R2 and R3 are H, substituted or unsubstituted C1 to C6 alkyl, C1 to C6 perfluoroalkyl, substituted or unsubstituted C2 to C6 alkenyl, substituted or unsubstituted C2 to C6 alkynyl, substituted or unsubstituted C3 to C6 cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic; or R2 and R3 are fused to form spirocyclic rings; R4 is NHR7, OR7, NHSO2R7, or OSO2R7; Q is O, S, NR8, or CR9R10; or a pharmaceutically acceptable salt, ester, or prodrug thereof. Such compounds are useful as progesterone receptor modulators and for treating progesterone receptor related conditions

  提供了具有公式I结构的化合物。在公式I中，R1是H，OH，取代或未取代的C1至C3烷基，C1至C3全氟烷基或COR6; R6是H，取代或未取代的C1至C4烷基，芳基，取代或未取代的C1至C4烷氧基，取代或未取代的C1至C3氨基烷基; R2和R3是H，取代或未取代的C1至C6烷基，C1至C6全氟烷基，取代或未取代的C2至C6烯基，取代或未取代的C2至C6炔基，取代或未取代的C3至C6环烷基，取代或未取代的芳基，或取代或未取代的杂环基; 或者R2和R3融合形成螺环状环; R4是NHR7，OR7，NHSO2R7或OSO2R7; Q是O，S，NR8或CR9R10; 或其药学上可接受的盐，酯或前药。这些化合物可用作孕激素受体调节剂，并用于治疗孕激素受体相关疾病。
• Neue Imidazo-benzoxazinone, ihre Herstellung und diese Verbindungen enthaltende Arzneimittel
  申请人：Dr. Karl Thomae GmbH

  公开号：EP0263352A1

  公开（公告）日：1988-04-13

  Die Erfindung betrifft neue Imidazo-benzoxazinone der Formel in der R. eine gegebenenfalls durch eine Phenyl-oder Pyridylgruppe substituierte Alkylgruppe, eine gegebenenfalls durch eine Alkylgruppe substituierte Mercaptogruppe, eine Vinylengruppe, die endständig durch eine Phenyl-oder Pyridylgruppe substituiert ist. eine gegebenenfalls durch ein Halogenatom, eine Hydroxy-, Alkoxy-, Mercapto-, Alkylmercapto-, Alkylsulfinyl-, Alkylsulfonyl-, Cyano-. Amino-oder Nitrogruppe substituierte Phenylgruppe, wobei eine Hydroxyphenylgruppe zusätzlich durch eine oder zwei Alkylgruppen oder eine Aminophenylgruppe durch ein oder zwei Halogenatome substituiert sein kann, eine durch Halogenatome, Hydroxy-, Alkoxy-, Mercapto-, Alkylmercapto-, Alkylsulfinyl-oder Alkylsulfonylgruppen disubstituierte Phenylgruppe, wobei die Substituenten des Phenylkerns gleich oder verschieden sein können, einen über ein Kohlenstoffatom gebundenen 5-oder 6-gliedrigen heteroaromatischen Ring, welcher ein Sauerstoff-, Schwefel-oder Stickstoffatom, zwei oder drei Stickstoffatome oder ein Stickstoffatom und ein Sauerstoff-oder Schwefelatom enthält, an den zusätzlich über zwei benachbarte Kohlenstoffatome eine oder zwei 1,4-Butadienylgruppen gebunden sein können, wobei im Falle der Pyridine diese zusätzlich durch eine Amino-, Alkanoylamino-oder Morpholinogruppe oder durch zwei Halogenatome oder durch ein Halogen atom und eine Amino-oder Morpholinogruppe substituiert sein können, oder einen über einen Kohlenstoffatom gebundenen 5-bis 7-gliedrigen gesättigten Imino-, N-Alkyl-imino-oder N-Alkanoyl-imino-alkylenring in dem eine Methylengruppe in 4-Stellung durch eine Imino-, Alkylimino-oder Alkanoyliminogruppe oder eine -CH2CH2-Gruppe durch eine -NH-CO-Gruppe ersetzt sein kann, wobei die CO-Gruppe dieser -NH-CO-Gruppe mit dem bereits vorhandenen N-Atom verknüpft sein muß, und außerdem alle vorstehend erwähnten heteroaromatischen Ringe und gesättigten Ringe durch eine Alkylgruppe substituiert sein können, R2 ein Wasserstoffatom, eine gegebenenfalls ab Position 2 durch eine Hydroxy-oder Alkoxygruppe substituierte Alkylgruppe oder eine Phenylalkylgruppe, R3 und R4, die gleich oder verschieden sein können. Wasserstoffatome oder Alkylgruppe bedeuten, deren 3H-Tautomere und deren Säureadditionssalze, insbesondere für die pharmazeutische Anwendung deren physiologisch verträgliche Säureadditionssalze mit anorganischen oder organischen Säuren, welche wertvolle pharmakologische Eigenschaften aufweisen, insbesondere antithrombotische und cardiovasculäre Eigenschaften. Die neuen Verbindungen lassen sich nach bekannten Methoden herstellen.

  本发明涉及新型咪唑-苯并噁嗪酮，其式如下 其中 R.是任选被苯基或吡啶基取代的烷基、任选被烷基取代的巯基、被苯基或吡啶基末端取代的乙烯基、任选被卤素原子取代的苯基、羟基、烷氧基、巯基、烷基巯基、烷基亚磺酰基、烷基磺酰基、氰基、氨基或硝基，其中羟基苯基可另外被一个或两个烷基或氨基苯基取代。氨基或硝基，其中羟基苯基可另外被一个或两个烷基取代，或氨基苯基可被一个或两个卤素原子取代，苯基可被卤素原子、羟基、烷氧基、巯基、烷基巯基、烷基亚磺酰基或烷基磺酰基取代，其中苯基核的取代基可以相同或不同、通过一个碳原子键合的 5 或 6 元杂芳环，该环含有一个氧原子、硫原子或氮原子、两 个或三个氮原子或一个氮原子和一个氧原子或硫原子，此外还可通过相邻的两个 碳原子键合一个或两个 1,4-丁二烯基团、在吡啶的情况下，这些基团可另外被一个氨基、烷酰氨基或吗啉基取代，或被两个卤素原子取代，或被一个卤素原子和一个氨基或吗啉基取代，或被一个5-7元饱和亚氨基、N-烷基亚氨基或N-烷酰亚氨基烷基环通过一个碳原子结合，其中4-位上的亚甲基被亚氨基、N-烷基亚氨基或N-烷酰亚氨基烷基取代、烷基亚氨基或烷酰亚胺基团或 -CH2CH2 基团可被 -NH-CO 基团取代，其中 -NH-CO 基团的 CO 基团必须与已存在的 N 原子相连，此外，所有上述杂芳环和饱和环均可被烷基取代、 R2 是氢原子、从第 2 位开始被羟基或烷氧基或苯基烷基取代的烷基、 R3 和 R4 可以相同或不同。氢原子或烷基指的是它们的 3H 同系物及其酸加成盐，特别是用于医药用途的它们与无机酸或有机酸的生理相容的酸加成盐，它们具有宝贵的药理特性，特别是抗血栓和心血管特性。 这些新化合物可以用已知的方法生产。