ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(4-methylthiazol-2-yl)-2-naphthalenyl)ethynyl]benzoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(4-methylthiazol-2-yl)-2-naphthalenyl)ethynyl]benzoate
• 英文别名: Ethyl 4-[5,6-dihydro-5,5-dimethyl-8-(4-methylthiazol-2-yl)-2-naphthalenyl]ethynylbenzoate；ethyl 4-[2-[5,5-dimethyl-8-(4-methyl-1,3-thiazol-2-yl)-6H-naphthalen-2-yl]ethynyl]benzoate
• 化学式: C₂₇H₂₅NO₂S
• 分子量: 427.567
• InChiKey: LZFMZZSPBKLMHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  67.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(4-methylthiazol-2-yl)-2-naphthalenyl)ethynyl]benzoate 、 sodium hydroxide 在 Brine 、 Sodium sulfate-III 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 4-[(5,6-Dihydro-5,5-dimethyl-8-(4-methylthiazol-2-yl)-2-naphthalenyl)ethynyl]benzoic acid
  参考文献：
  名称：

  Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities

  摘要：

  取代芳基和取代苯并吡喃、苯并硫喹啉、1,2-二氢喹啉和5,6-二氢萘衍生物具有视黄酸负性激素和/或拮抗剂样生物活性。发明的RAR拮抗剂可用于哺乳动物，包括人类，以防止或减轻RAR激动剂对结合受体位点的作用。具体而言，RAR激动剂与视黄酸药物一起给予或联合给予，以防止或改善视黄酸或维生素A或维生素A前体引起的毒性或副作用。视黄酸负性激素可用于增强其他视黄酸和核受体激动剂的活性。例如，称为AGN 193109的视黄酸负性激素在体外转录激活实验中有效提高了其他视黄酸和类固醇激素的有效性。此外，转录激活实验可用于鉴定具有负性激素活性的化合物。这些实验基于负性激素降低嵌合视黄酸受体活性的能力。

  公开号：

  US06228848B1

文献信息

• Synthesis and use of retinoid compounds having negative hormone and/or
  申请人：Allergan Sales, Inc.

  公开号：US05877207A1

  公开（公告）日：1999-03-02

  Aryl-substituted and aryl and (3-oxo-1-propenly)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors engineered to possess a constitutive transcription activator domain.

  芳基取代和芳基和（3-氧代-1-丙烯基）取代的苯并吡喃、苯并硫吡喃、1,2-二氢喹啉和5,6-二氢萘衍生物具有视黄醇负性激素和/或拮抗剂样生物活性。所发明的RAR拮抗剂可用于哺乳动物，包括人类，以防止或减轻RAR激动剂对结合受体位点的作用。具体而言，RAR激动剂可与视黄醇药物一起给予或联合给予，以防止或减轻视黄醇或维生素A或维生素A前体引起的毒性或副作用。视黄醇负性激素可用于增强其他视黄醇和核受体激动剂的活性。例如，名为AGN 193109的视黄醇负性激素在体外转录激活实验中有效增加了其他视黄醇和类固醇激素的效力。此外，转录激活实验可用于识别具有负性激素活性的化合物。这些实验基于负性激素调节具有构成转录激活子结构域的嵌合视黄醇受体活性的能力。
• [EN] BENZOPYRAN AND BENZOTHIOPYRAN DERIVATIVES HAVING RETINOID ANTAGONIST-LIKE ACTIVITY<br/>[FR] DERIVES DE BENZOPYRANE ET BENZOTHYOPYRANE PRESENTANT UNE ACTIVITE RETINOÏDE DE TYPE ANTAGONISTE
  申请人：ALLERGAN SALES, INC.

  公开号：WO1999033821A1

  公开（公告）日：1999-07-08

  (EN) 2,2-Dialkyl- 4-aryl-substituted benzopyran and benzothiopyran derivatives of formula (I) where the symbols have the meaning described in the specification, have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action or RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists.(FR) L'invention concerne des dérivés de 2,2-dialkyl-benzopyrane et benzothiopyrane à substitution 4-aryl de formule (I), dont les symboles sont définis dans le descriptif. Ces dérivés présentent des activités biologiques rétinoïdes de type antagonistes et/ou hormones négatives. Les antagonistes de RAR de l'invention peuvent être administrés aux mammifères, y compris aux humains, pour prévenir ou réduire l'action d'antagonistes de RAR sur les sites récepteurs liés. En particulier, les agonistes de RAR sont administrés ou co-administrés avec des médicaments rétinoïdes pour empêcher ou atténuer la toxicité ou les effets secondaires des rétinoïdes, de la vitamine A ou des précurseurs de la vitamine A. Les hormones négatives rétinoïdes peuvent être utilisées pour renforcer les activités d'autres rétinoïdes et celles d'agonistes de récepteurs nucléaires.

  2,2-二烷基-4-芳基取代苯并吡喃和苯并噻吩的衍生物，其化学式为(I)，其中符号的含义在说明书中描述，具有视黄醇负性激素和/或拮抗剂样生物活性。发明的RAR拮抗剂可用于哺乳动物，包括人类，以防止或减少RAR激动剂对结合受体位点的作用。具体而言，RAR激动剂与视黄醇药物一起给予或联合给予，以防止或缓解视黄醇或维生素A或维生素A前体引起的毒性或副作用。视黄醇负性激素可用于增强其他视黄醇和核受体激动剂的活性。
• Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities
  申请人：——

  公开号：US20030219832A1

  公开（公告）日：2003-11-27

  Aryl-substituted and aryl and (3-oxo-1-propenly)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors engineered to possess a constitutive transcription activator domain.

  取代芳基和取代芳基和（3-氧代-1-丙烯基）基苯并吡喃、苯并硫吡喃、1,2-二氢喹啉和5,6-二氢萘衍生物具有视黄醛受体负性激素和/或拮抗剂样的生物活性。发明的RAR拮抗剂可用于哺乳动物，包括人类，以防止或减少RAR激动剂对结合受体位点的作用。具体而言，RAR激动剂与视黄醇药物一起使用或联合使用，以防止或缓解视黄醇或维生素A或维生素A前体引起的毒性或副作用。视黄醛负性激素可用于增强其他视黄醇和核受体激动剂的活性。例如，名为AGN 193109的视黄醛负性激素在体外转录激活测定中有效地增加了其他视黄醇和类固醇激素的效力。此外，转录激活测定可用于鉴定具有负性激素活性的化合物。这些测定基于负性激素降调节嵌合视黄醛受体活性的能力。
• Method of identifying negative hormone and/or antagonist activities
  申请人：Allergan, Inc.

  公开号：US05776699A1

  公开（公告）日：1998-07-07

  Aryl-substituted and aryl and (3-oxo-1-propenly)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors engineered to possess a constitutive transcription activator domain.

  取代芳基和芳基和(3-氧代-1-丙烯基)-取代苯并吡喃、苯并硫喹啉、1,2-二氢喹啉和5,6-二氢萘衍生物具有视黄酸负性激素和/或拮抗剂样生物活性。发明的RAR拮抗剂可用于哺乳动物，包括人类，以防止或减少RAR激动剂对结合受体位点的作用。具体而言，RAR激动剂与视黄酸药物一起或同时投与，以防止或减轻由视黄酸或视黄酸前体引起的毒性或副作用。视黄酸负性激素可用于增强其他视黄酸和核受体激动剂的活性。例如，名为AGN 193109的视黄酸负性激素在体外转录激活实验中有效增强了其他视黄酸和类固醇激素的效果。此外，转录激活实验可用于鉴定具有负性激素活性的化合物。这些实验基于负性激素通过下调带有组成性转录激活子域的嵌合视黄酸受体的活性的能力。
• Synthesis and use of retinoid compounds having negative hormone and/or anatgonist activities
  申请人：Allergan, Inc.

  公开号：US06469028B1

  公开（公告）日：2002-10-22

  Aryl-substituted and aryl and (3-oxo-1-propenly)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors engineered to possess a constitutive transcription activator domain.

  含芳基取代的苯并吡喃、苯并硫喹啉、1,2-二氢喹啉和5,6-二氢萘衍生物具有类激素对视黄醇受体(RAR)的负性调节和/或拮抗剂样生物活性。发明的RAR拮抗剂可用于哺乳动物，包括人类，以防止或减轻RAR激动剂对受体位点的作用。具体而言，RAR激动剂与视黄醇药物一起给予，以防止或减轻视黄醇或维生素A或维生素A前体引起的毒性或副作用。视黄醇负性激素可用于增强其他视黄醇和核受体激动剂的活性。例如，名为AGN 193109的视黄醇负性激素在体外转录激活试验中有效地增强了其他视黄醇和类固醇激素的效果。此外，转录激活试验可用于鉴定具有负性激素活性的化合物。这些试验基于负性激素调节人工合成的具有组成转录激活子结构域的嵌合型视黄醇受体的活性能力。