3-[3-Carboxy-2-methyl-1-[(Z)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydroanthracen-2-ylmethylene]-2(Z)-propenyl]benzoic acid | 161914-56-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 3-[3-Carboxy-2-methyl-1-[(Z)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydroanthracen-2-ylmethylene]-2(Z)-propenyl]benzoic acid
• 英文别名: (2Z,4Z)-3-methyl-4-(3-carboxyphenyl)-5-[(1,2,3,4-tetrahydro-1,1,4,4-tetramethyl)-6-anthracenyl]-2,4-pentadienoic acid；(2Z,4Z)-3-methyl-4-(3-carboxyphenyl)-5-[(1,2,3,4-tetrahydro-1,1,4,4-tetramethyl)-6-anthryl]-2,4-pentadienoic acid；3-((1Z,2Z)-3-Carboxy-2-methyl-1-((5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)methylene)-2-propen-1-yl)benzoic acid；3-[(1Z,3Z)-4-carboxy-3-methyl-1-(5,5,8,8-tetramethyl-6,7-dihydroanthracen-2-yl)buta-1,3-dien-2-yl]benzoic acid
• CAS: 161914-56-3
• 化学式: C₃₁H₃₂O₄
• 分子量: 468.593
• InChiKey: MSCWLMXCFHMGMN-SHUXQVCQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[3-Carboxy-2-methyl-1-[(Z)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydroanthracen-2-ylmethylene]-2(Z)-propenyl]benzoic acid 在 N-羟基丁二酰亚胺 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 生成 3-{(Z)-3-Carbamoyl-2-methyl-1-[1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-anthracen-2-yl)-meth-(E)-ylidene]-allyl}-benzamide
  参考文献：
  名称：

  Dicarboxylic acid inhibitors of phospholipase A2

  摘要：

  Ten diacids were synthesized via a simple regio- and stereoselective aldol reaction. All of these compounds were good to excellent inhibitors of 14 kDa human platelet PLA(2), and many of these derivatives displayed activity in a phorbol-ester induced mouse ear edema assay. One of the new compounds reported here was selected for further development as a potential antipsoriasis agent. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00110-8
• 作为产物：
  描述：

  5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-anthracene-2-carbaldehyde 、 ethyl 3-(4-ethoxy-2-methyl-4-oxobut-2-enyl)benzoate 在 potassium tert-butylate 、 水 作用下， 生成 3-[3-Carboxy-2-methyl-1-[(Z)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydroanthracen-2-ylmethylene]-2(Z)-propenyl]benzoic acid
  参考文献：
  名称：

  Dicarboxylic acid inhibitors of phospholipase A2

  摘要：

  Ten diacids were synthesized via a simple regio- and stereoselective aldol reaction. All of these compounds were good to excellent inhibitors of 14 kDa human platelet PLA(2), and many of these derivatives displayed activity in a phorbol-ester induced mouse ear edema assay. One of the new compounds reported here was selected for further development as a potential antipsoriasis agent. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00110-8

文献信息

• Alicyclic phospholipase A2 inhibitors
  申请人：Bristol-Myers Company

  公开号：EP0629604A2

  公开（公告）日：1994-12-21

  Compounds of Formula I: wherein the bonds between C₂ and C3 and/or between C₄ and C₅ are unsaturated; X = COOH, H, F, Cl, Br, I, COOR'', CONH₂, COR''', CHO, CH₂OH, CH₂OR''', OH, OR''', CF₃, C1-6 alkyl, C1-6 alkenyl, C1-6 haloalkyl, NO₂, P(O)(OH)₂, SO₂H, or SO₃H; R = substituted or unsubstituted alkyl, aryl, arylalkyl, alkenyl, or arylalkenyl groups, with the proviso that each of these groups must have 6 or more carbons (preferably 6 to 30) and R cannot be R' = H or C1-6 alkyl; R'' = H, C1-6 alkyl, C(R³)₂OC(O)R⁴, CH₂CH₂NR⁵R⁶, CH₂CH₂CH₂NR⁵R⁶, CH₂C(O)N(R⁶)₂, or other groups yielding physiologically hydrolyzable esters; R''' = C1-6 alkyl; R³ = H, CH₃, C₂H₅, CH₃CH₂CH₂ (with R³'s being the same or different); R⁴ = C6-12 aryl, C1-7 linear, branched or cyclic alkyl, or C1-7 linear, branched or cyclic alkoxy; R⁵ = R⁶, or when linked with R⁶, is a C₃-C₆ cycloalkyl or a -CH₂CH₂OCH₂CH₂-group; and R⁶ = C1-3 alkyl; and pharmaceutically-acceptable salts thereof are effective phospholipase A₂ (PLA₂) inhibitors.

  式 I 的化合物： 其中 C₂ 与 C3 之间和/或 C₄ 与 C₅ 之间的键为不饱和键； X = COOH、H、F、Cl、Br、I、COOR''、CONH₂、COR'''、CHO、CH₂OH、CH₂OR'''、OH、OR'''、CF₃、C1-6 烷基、C1-6 烯基、C1-6 卤代烷基、NO₂、P(O)(OH)₂、SO₂H 或 SO₃H； R = 取代或未取代的烷基、芳基、芳烷基、烯基或芳烷烯基，但这些基团都必须具有 6 个或更多的碳原子（最好是 6 至 30 个），且 R 不能是 R' = H 或 C1-6 烷基； R''=H、C1-6 烷基、C(R³)₂OC(O)R⁴、CH₂CH₂NR⁵R⁶、CH₂CH₂CH₂NR⁵R⁶、CH₂C(O)N(R⁶)₂ 或其他可产生生理性水解酯的基团； R''' = C1-6 烷基； R³ = H、CH₃、C₂H₅、CH₃CH₂CH₂（R³'s 相同或不同）； R⁴ = C6-12 芳基，C1-7 直链、支链或环状烷基，或 C1-7 直链、支链或环状烷氧基； R⁵ = R⁶，或当与 R⁶ 连接时，为 C₃-C₆ 环烷基或-CH₂CH₂OCH₂CH₂基团；以及 R⁶ = C1-3 烷基； 及其药学上可接受的盐是有效的磷脂酶 A₂（PLA₂）抑制剂。
• Medicaments for treating vascular leak syndrome
  申请人：Bristol-Myers Squibb Company

  公开号：EP0701817A2

  公开（公告）日：1996-03-20

  A novel method for preventing, stabilizing or causing regression of vascular leak syndrome is disclosed. The method comprises administering to a patient in need thereof a compound selected from the group consisting of a corticosteroid, a non-steroidal anti-inflammatory agent, 15-deoxyspergualin and related compounds, and phospholipase A₂ inhibitors.

  本发明公开了一种预防、稳定或导致血管渗漏综合征消退的新方法。该方法包括向有需要的患者施用选自皮质类固醇、非甾体抗炎剂、15-脱氧鸭嘴花碱及相关化合物和磷脂酶 A₂抑制剂的化合物。
• Methods and compositions for enhancing skin permeation of drugs using permeation enhancers
  申请人：Bristol-Myers Squibb Company

  公开号：EP0857488A2

  公开（公告）日：1998-08-12

  The invention provides methods and means for enhancing the epidermal, transdermal and dermal permeation of a topically applied pharmacologically active agent (e.g., a drug or medicament) which has a low rate of skin penetration in the absence of a permeation enhancer and which is unstable and degrades during long-term storage with particular permeation enhancers. Also provided by the invention are methods and means to increase the skin penetration of a pharmacologically active agent which has a normally low rate of skin permeation and causes the instability and degradation of a permeation enhancer with which it is combined over a long period of time. Provided by the invention are at least one first composition containing a drug, a pharmaceutically acceptable salt, chemical derivative or formulation thereof, in a dermatologically acceptable vehicle, and at least one second composition containing a permeation enhancer in an acceptable vehicle. The compositions are physically separated until application to a body or skin surface and are topically applied, either at the same time, or sequentially within a short time of each other, and mixed or blended to form a final active composition, preferably on the skin. In addition, a premixture of the compositions can be made and applied to the skin in accordance with the invention. The invention allows a therapeutically effective amount of drug to be delivered into the skin and systemic circulation and provides significant enhancement of a drug's otherwise low level of skin permeation by the action of permeation enhancer in the active composition at the point of use.

  本发明提供了提高局部应用的药理活性剂（如药物或药剂）的表皮、透皮和真皮渗透 的方法和手段，这种药理活性剂在没有渗透促进剂的情况下皮肤渗透率较低，在与特定 的渗透促进剂长期贮存期间不稳定并发生降解。本发明还提供了提高药理活性剂的皮肤渗透率的方法和手段，这种药理活性剂的皮肤渗透率通常较低，与渗透促进剂长期结合会导致其不稳定和降解。本发明提供了至少一种第一组合物，其中含有一种药物、其药学上可接受的盐、化学衍生物或制剂，并置于皮肤病学上可接受的载体中；以及至少一种第二组合物，其中含有一种渗透促进剂，并置于可接受的载体中。这些组合物在施用到身体或皮肤表面之前是物理分离的，可以同时施用，也可以在短时间内依次施用，然后混合或调配形成最终的活性组合物，最好施用在皮肤上。此外，还可以根据本发明制作组合物的预混合物，并涂抹在皮肤上。本发明可将治疗有效量的药物输送到皮肤和全身循环中，并在使用时通过活性组合物中渗透促进剂的作用，显著提高药物原本较低的皮肤渗透水平。
• COMPOUNDS FOR THE TREATMENT OF COVID-19
  申请人：Dompe' Farmaceutici S.P.A.

  公开号：EP3875078A1

  公开（公告）日：2021-09-08

  The present invention relates to compounds that are able to inhibt 3CL protease of COVID-19 virus, SARS-Cov-2

  本发明涉及能够抑制 COVID-19 病毒、SARS-Cov-2 病毒的 3CL 蛋白酶的化合物。
• Compositions for enhancing skin permeation of drugs using permeation enhancers
  申请人：Bristol-Myers Squibb Company

  公开号：EP0857488B1

  公开（公告）日：2004-07-21