5-[2-(3,5,5,8,8-Pentamethyl-6,7-dihydronaphthalen-2-yl)prop-1-enyl]thiophene-2-carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 5-[2-(3,5,5,8,8-Pentamethyl-6,7-dihydronaphthalen-2-yl)prop-1-enyl]thiophene-2-carboxylic acid
• 化学式: C₂₃H₂₈O₂S
• 分子量: 368.5
• InChiKey: QPAMXNZWXFZISY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  3

文献信息

• [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。
• Treatment o tumors with compounds having RXR retinoid receptor agoinst activity
  申请人：ALLERGAN, INC.

  公开号：EP0909560A2

  公开（公告）日：1999-04-21

  The invention provides a pharmaceutical composition suitable for inducing apoptotic death of tumor cells in a mammal suffering from a tumor, the pharmaceutical composition including a pharmaceutically acceptable excipient and an active compound which has the biological property that the compound is an agonist of RXR retinoid receptors. The active compound preferably has the formula: wherein R1 is C1-6 alkyl, C1, Br, or I; R2 is H, C1-6 alkyl, C1, Br, or I; R3 is C1-6 alkyl, C1, Br, I, OR11, SR11, OCOR11, SCOR11, NH2, NHR11, N(R11)2, NHCOR11, or NR11-COR11; the R5 groups independently are H, C1-6 alkyl, C1, Br, I, C1-6 alkoxy or C1-6 thioalkoxy; the R6 groups independently are H or C1-6 alkyl; A is (CH2)n is 0-5, lower branched chain alkyl having 3 to 6 carbons, cycloalkyl having 3 to 6 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, alkynyl having 2 to 6 carbons and 1 or 2 triple bonds, and B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR8, CONR9R10, -CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR130, -COR7, CR7(OR12)2, or CR7OR13O, where R7, is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R8 is an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R8 is phenyl or C1-6 alkylphenyl, R9 and R10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or phenyl or C1-6 alkylphenyl, R11 is alkyl or 1 to 10 carbons, phenyl or C1-6 alkylphenyl, R12 is C1-6 alkyl, and R13 is divalent alkyl radical of 2 - 5 carbons.

  本发明提供了一种适用于诱导患有肿瘤的哺乳动物体内肿瘤细胞凋亡的药物组合物，该药物组合物包括一种药学上可接受的赋形剂和一种活性化合物，该活性化合物的生物学特性是该化合物是 RXR 视黄醇受体的激动剂。活性化合物最好具有如下式子 式中 R1 是 C1-6 烷基、C1、Br 或 I； R2 是 H、C1-6 烷基、C1、Br 或 I； R3 是 C1-6 烷基、C1、Br、I、OR11、SR11、OCOR11、SCOR11、NH2、NHR11、N(R11)2、NHCOR11 或 NR11-COR11； R5 基团分别为 H、C1-6 烷基、C1、Br、I、C1-6 烷氧基或 C1-6 硫代烷氧基； R6 基团各自为 H 或 C1-6 烷基； A 是 (CH2)n 为 0-5 的碳原子、具有 3-6 个碳原子的低支链烷基、具有 3-6 个碳原子的环烷基、具有 2-6 个碳原子和 1-2 个双键的烯基、具有 2-6 个碳原子和 1-2 个三键的炔基，以及 B 是氢、COOH 或其药学上可接受的盐、COOR8、CONR9R10、-CH2OH、CH2OR11、CH2OCOR11、CHO、CH(OR12)2、CHOR130、-COR7、CR7(OR12)2 或 CR7OR13O，其中 R7 是含 1 至 5 个碳原子的烷基、环烷基或烯基，R8 是含 1 至 10 个碳原子的烷基或含 5 至 10 个碳原子的环烷基、或 R8 是苯基或 C1-6 烷基苯基，R9 和 R10 独立地是氢、含 1 至 10 个碳原子的烷基或含 5 至 10 个碳原子的环烷基或苯基或 C1-6 烷基苯基，R11 是烷基或含 1 至 10 个碳原子的苯基或 C1-6 烷基苯基，R12 是 C1-6 烷基，R13 是含 2 - 5 个碳原子的二价烷基。
• Treatment of tumors with compounds having RxR retinoid receptor agonist activity
  申请人：ALLERGAN, INC.

  公开号：EP1159961A2

  公开（公告）日：2001-12-05

  The invention provides the use of a compound which has retinoid like activity and is an agonist of RXR retinoid receptors, for the manufacture of a medicament for inducing apoptotic death of tumor cells in a host mammal thereby to treat the tumor.

  本发明提供了一种具有类视黄醇活性且是 RXR 视黄醇受体激动剂的化合物，用于制造一种药物，诱导宿主哺乳动物体内的肿瘤细胞凋亡，从而治疗肿瘤。
• Treatment for age-related macular degeneration (AMD)
  申请人：——

  公开号：US20030162758A1

  公开（公告）日：2003-08-28

  The present invention addresses the treatment of age-related macular degeneration using regulation of pathogenic mechanisms similar to atherosclerosis. In further specific embodiments, reverse cholesterol transport components, such as transporters and HDL fractions, are utilized as diagnostic and therapeutic targets for age-related macular degeneration. In a specific embodiment, the lipid content of the retinal pigment epithelium, and/or Bruch's membrane is reduced.

  本发明利用与动脉粥样硬化类似的致病机制的调节来治疗老年性黄斑变性。在更具体的实施方案中，反向胆固醇转运成分，如转运体和高密度脂蛋白组分，被用作老年性黄斑变性的诊断和治疗靶标。在一个具体的实施方案中，视网膜色素上皮和/或布鲁氏膜的脂质含量降低。