3-氟-4-{[羟基(5,5,8,8-四甲基-5,6,7,8-四氢-2-萘基)乙酰基]氨基}苯甲酸 | 185629-22-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-氟-4-{[羟基(5,5,8,8-四甲基-5,6,7,8-四氢-2-萘基)乙酰基]氨基}苯甲酸
• 英文名称: 3-Fluoro-4-[[2-hydroxy-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)acetyl]amino]benzoic acid
• CAS: 185629-22-5
• 化学式: C₂₃H₂₆FNO₄
• 分子量: 399.5
• InChiKey: AANFHDFOMFRLLR-UHFFFAOYSA-N

物化性质

• 沸点：
  590.9±50.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  86.6
• 氢给体数：
  3
• 氢受体数：
  5

文献信息

• NOVEL AND SPECIFIC INHIBITORS OF CYTOCHROME P450 26 RETINOIC ACID HYDROXYLASE
  申请人：UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION

  公开号：US20160200703A1

  公开（公告）日：2016-07-14

  The present disclosure is generally directed to compositions and methods for treating diseases that are ameliorated by the inhibition of CYP26 mediated retinoic acid metabolism. The compositions comprise compounds of formula (I). A repreid50000060307390 IB/345 nullsents aryl optionally substituted with one, two, three, or four groups that are each independently halogen, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, —NH 2 , —NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl) 2 , —OH, C 1 -C 6 alkoxy, and C 1 -C 6 haloalkoxy; X is a bond, —CH 2 —, —CHR 5 —, —C═CHR 4 —, —NR 4 —, —N═O—R 4 —, —O—, —S—, —SO—, —SO 2 —, —C(O)—, or —C(NR 4 )—, or X is of formula (a), (b) or (c), wherein each n is independently 1, 2, or 3; each R 4 is independently hydrogen or C 1-6 alkyl; R 5 is independently hydrogen, C 1-6 alkyl, or —OR 6 , where R 6 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyL C 3-12 cycloalkyl, heterocyclyl, aryl, arylC 1-6 alkyl, heteroaryl, or heteroarylC 1-6 alkyl; Y is C 1-6 alkylene, C 2-6 alkenylene, or C 2-6 alkylylene moiety.

  本公开涉及的是组合物和治疗方法，用于治疗通过抑制CYP26介导的视黄酸代谢而改善的疾病。这些组合物包括公式（I）的化合物。其中，芳基可选地取代为一个、两个、三个或四个基团，每个基团独立地为卤素、氰基、硝基、C1-6烷基、C1-6卤代烷基、-NH2、-NH（C1-C6烷基）、-N（C1-C6烷基）2、-OH、C1-C6烷氧基和C1-C6卤代烷氧基；X为键，-CH2-，-CHR5-，-C═CHR4-，-NR4-，-N═O-R4-，-O-，-S-，-SO-，-SO2-，-C（O）-或-C（NR4）-，或X为公式（a）、（b）或（c），其中每个n独立地为1、2或3；每个R4独立地为氢或C1-6烷基；每个R5独立地为氢、C1-6烷基或-OR6，其中R6选自由氢基、C1-6烷基、C2-6烯基、C2-6炔基、C3-12环烷基、杂环基、芳基、芳基C1-6烷基、杂芳基或杂芳基C1-6烷基；Y为C1-6烷基、C2-6烯基或C2-6烷基亚基。
• THERAPEUTIC BENEFIT OF SUBOPTIMALLY ADMINISTERED CHEMICAL COMPOUNDS
  申请人：BROWN Dennis M.

  公开号：US20160045502A1

  公开（公告）日：2016-02-18

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to mustard-based alkylating agents such as uracil mustard and analogs, derivatives, or prodrugs thereof, including 6-methyluracil mustard and 6-ethyluracil mustard.

  本发明描述了一种改善先前受到治疗性能不佳限制的治疗剂的治疗效果的方法和组合物，通过改善单药疗法的功效或减少副作用。这种方法和组合物特别适用于芥子碱基烷基化剂，例如尿嘧啶芥和其类似物、衍生物或前药，包括6-甲基尿嘧啶芥和6-乙基尿嘧啶芥。
• RARy-specific retinobenzoic acid derivatives
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0747347A1

  公开（公告）日：1996-12-11

  Retinoid-like activity is exhibited by compounds of the formula wherein X is F, Cl, OH or CH3, Y is H or F, R1-R6 are each independently hydrogen or C1-C6 alkyl, n is an integer of 1 to 4 and R7 is hydrogen or a carboxyl-protecting group, and pharmaceutically acceptable salts thereof. The compounds of formula I selectively interact with the retinoic acid subtype RARγ and have been found to lack the liver toxicity associated with systemic administration of non-selective retinoids.

  式中的化合物具有类视黄醇活性 其中 X 是 F、Cl、OH 或 CH3，Y 是 H 或 F，R1-R6 独立地分别是氢或 C1-C6 烷基，n 是 1 至 4 的整数，R7 是氢或羧基保护基团，及其药学上可接受的盐类。式 I 的化合物可选择性地与视黄酸亚型 RARγ 发生作用，并且不存在与全身给药非选择性视黄酸相关的肝毒性。
• Use of Vitamin D3 agonist in a mammalian model for atopic diseases and of Vitamin D3 antagonists for the treatment of atopic diseases
  申请人：Association pour la recherche à l'IGBMC (ARI)

  公开号：EP1891944A1

  公开（公告）日：2008-02-27

  The present invention concerns a method for generating a human atopic disease-like phenotype, preferably an atopic dermatitis (AD)-like phenotype in a mammal comprising administrating to said mammal at least one compound selected in the group comprising the physiologically active vitamin D3 (1α,25 (OH)2 D3) and agonistic analogs thereof. The present invention also concerns a method for treating and/or preventing an atopic disease in a patient comprising administrating to said patient an effective amount of at least one vitamin D3 antagonist.

  本发明涉及一种在哺乳动物中产生人类特应性疾病样表型，优选特应性皮炎（AD）样表型的方法，包括向所述哺乳动物施用至少一种选自生理活性维生素D3（1α,25 (OH)2 D3）及其激动类似物的化合物。本发明还涉及一种治疗和/或预防患者特应性疾病的方法，包括向所述患者施用有效量的至少一种维生素 D3 拮抗剂。
• THERAPEUTIC AGENT FOR KERATOCONJUNCTIVE DISORDERS
  申请人：Yamaguchi University

  公开号：EP2918290A1

  公开（公告）日：2015-09-16

  The present invention addresses the problem of providing a novel therapeutic agent for keratoconjunctive disorders. As a means for solving the problem, a therapeutic agent for keratoconjunctive disorders which contains a RARγ agonist as an active ingredient is provided. The therapeutic agent exhibits an excellent ameliorating effect in a keratoconjunctive disorder model, and is therefore useful as a therapeutic agent for keratoconjunctive disorders such as corneal ulcer, corneal epithelial abrasion, keratitis, dry eye, conjunctivitis, chronic superficial keratitis, corneal erosion, persistent corneal disorders, superficial punctate keratopathy, corneal epithelial defects, conjunctival epithelial defects, keratoconjunctivitis sicca, superior limbic keratoconjunctivitis, filamentary keratoconjunctivitis, infectious keratitis, noninfectious keratitis, infectious conjunctivitis and noninfectious conjunctivitis. The therapeutic agent is also useful as a therapeutic agent for corneal scarring and conjunctival scarring both associated with keratoconjunctive disorders.

  本发明要解决的问题是提供一种新型的角结膜病治疗剂。作为解决问题的一种方法，本发明提供了一种角膜结膜病治疗剂，其活性成分中含有一种 RARγ 激动剂。该治疗剂在角膜结膜疾病模型中表现出极佳的改善效果，因此可用作角膜结膜疾病的治疗剂，如角膜溃疡、角膜上皮擦伤、角膜炎、干眼症、结膜炎、慢性浅表角膜炎、角膜糜烂、持续性角膜病变、浅表点状角膜病、角膜上皮缺损、结膜上皮缺损、固执性角膜结膜炎、上肢角膜结膜炎、丝状角膜结膜炎、感染性角膜炎、非感染性角膜炎、感染性结膜炎和非感染性结膜炎。这种治疗剂还可用于治疗与角结膜炎相关的角膜瘢痕和结膜瘢痕。