6-(Trifluoromethyl)-2,2-dimethylchromene | 130199-77-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-(Trifluoromethyl)-2,2-dimethylchromene
• 英文别名: 6-trifluoromethyl-2,2-dimethylchromene；2H-1-Benzopyran, 2,2-dimethyl-6-(trifluoromethyl)-；2,2-dimethyl-6-(trifluoromethyl)chromene
• CAS: 130199-77-8
• 化学式: C₁₂H₁₁F₃O
• 分子量: 228.214
• InChiKey: VQJZNMGEOWWDIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(Trifluoromethyl)-2,2-dimethylchromene 在 氢氧化钾 、 N-溴代丁二酰亚胺(NBS) 、 水 、 sodium hydride 作用下， 以 乙醚 、 二甲基亚砜 为溶剂， 反应 1.0h， 生成 1-((3R,4S)-3-Hydroxy-2,2-dimethyl-6-trifluoromethyl-chroman-4-yl)-pyrrolidin-2-one
  参考文献：
  名称：

  Variation in the aromatic ring of cromakalim: antihypertensive activity of pyranopyridines and 6-alkyl-2H-1-benzopyrans

  摘要：

  The synthesis and antihypertensive activity in the spontaneously hypertensive rat of two new series of analogues related to cromakalim (1) are described. In the first series, where the benzopyran nucleus has been replaced by a pyranopyridine nucleus, the position of the nitrogen atom has been found to be critical for activity, and the most potent compounds are the pyrano[3,2-c]pyridines. In the second series, where the powerful electron-withdrawing cyano group of compound 1 has been replaced by alkyl and phenyl groups, the order of antihypertensive potency is ethyl, isopropyl, tert-butyl greater than propyl, cyclopentyl greater than methyl greater than phenyl.

  DOI：

  10.1021/jm00173a018
• 作为产物：
  描述：

  1-[(2-methylbut-3-yn-2-yl)oxy]-4-(trifluoromethyl)benzene 以 邻二氯苯 为溶剂， 生成 6-(Trifluoromethyl)-2,2-dimethylchromene
  参考文献：
  名称：

  Variation in the aromatic ring of cromakalim: antihypertensive activity of pyranopyridines and 6-alkyl-2H-1-benzopyrans

  摘要：

  The synthesis and antihypertensive activity in the spontaneously hypertensive rat of two new series of analogues related to cromakalim (1) are described. In the first series, where the benzopyran nucleus has been replaced by a pyranopyridine nucleus, the position of the nitrogen atom has been found to be critical for activity, and the most potent compounds are the pyrano[3,2-c]pyridines. In the second series, where the powerful electron-withdrawing cyano group of compound 1 has been replaced by alkyl and phenyl groups, the order of antihypertensive potency is ethyl, isopropyl, tert-butyl greater than propyl, cyclopentyl greater than methyl greater than phenyl.

  DOI：

  10.1021/jm00173a018

文献信息

• Analogs of the ATP-Sensitive Potassium (K_ATP) Channel Opener Cromakalim with in Vivo Ocular Hypotensive Activity
  作者：Uttio Roy Chowdhury、Kimberly B. Viker、Kristen L. Stoltz、Bradley H. Holman、Michael P. Fautsch、Peter I. Dosa

  DOI：10.1021/acs.jmedchem.6b00406

  日期：2016.7.14

  a normotensive rabbit model, with a significant difference in activity observed. No toxic effects on cell structure or alterations in morphology of the aqueous humor outflow pathway were observed after treatment with the most efficacious compound, (3S,4R)-2, suggesting that it is a strong candidate for development as an ocular hypotensive agent.

  ATP敏感性钾（K ATP）通道开放剂已成为治疗青光眼，降低动物模型和培养的人前眼节的眼内压（IOP）的潜在疗法。我们已经制备了K ATP的水溶性磷酸酯和二肽衍生物开沟剂cromakalim并评估了它们在体内降低IOP的能力。通常，在血压正常的小鼠模型中，每天给药一次，磷酸盐衍生物在降低IOP方面具有更强的化学稳定性和有效性。在正常血压的兔子模型中进一步评估了其中的两种磷酸盐衍生物，观察到活性存在显着差异。用最有效的化合物（3 S，4 R）-2处理后，未观察到对房水流出通道的细胞结构或形态变化有毒害作用，表明它是发展为眼压降压药的强力候选者。 。
• Benzopyran-type compounds
  申请人：BEECHAM GROUP PLC

  公开号：EP0375449B1

  公开（公告）日：1995-02-15
• Synthesis and antihypertensive activity of 3-[(substituted-carbonyl)amino]-2H-1-benzopyrans
  作者：Frederick Cassidy、John M. Evans、Michael S. Hadley、Adele H. Haladij、Patricia E. Leach、Geoffrey Stemp

  DOI：10.1021/jm00087a018

  日期：1992.5

  The synthesis and antihypertensive activity of a series of novel 3-[(subtituted-carbonyl)amino]-2H-1-benzopyran-4-ols, administered orally to spontaneously hypertensive rats, are described. Optimum activity in this series was observed for compounds with branched alkyl or branched alkylamino groups flanking the carbonyl or thiocarbonyl group (21, 31-33), which were approximately equipotent to cromakalim. Replacement of the 4-hydroxyl group by hydrogen, methoxy, or amino in this series only led to a slight reduction in potency. These observations are in marked contrast to the structure-activity relationships previously found for the 4-amidobenzopyran-3-ols. The antihypertensive activity of representative compounds 15 and 33 was attenuated by preatreatment with glibenclamide, and thus these compounds may belong to the series of drugs which have been classified as potassium channel activators.
• Osmium-Catalyzed Asymmetric Dihydroxylation of Cyclic Cis-Disubstituted Olefins
  作者：Zhi-Min Wang、Kiyomi Kakiuchi、K. Barry Sharpless

  DOI：10.1021/jo00102a008

  日期：1994.11

  A new class of cis-disubstituted olefins has been found to give good enantioselectivities in the asymmetric dihydroxylation reaction using the standard PHAL and PYR ligands, all the olefins are conjugated, and the reacting double bond is endocyclic in a 5-, 6-, 7-, or 8-membered ring.
• Relaxant activity of 4-amido-3,4-dihydro-2H-1-benzopyran-3-ols and 4-amido-2H-1-benzopyrans on guinea pig isolated trachealis
  作者：Derek R. Buckle、Jonathon R. S. Arch、Ashley E. Fenwick、Catherine S. V. Houge-Frydrych、Ivan L. Pinto、David G. Smith、Stephen G. Taylor、John M. Tedder

  DOI：10.1021/jm00173a019

  日期：1990.11

  A series of 4-amido-3,4-dihydro-2H-1-benzopyran-3-ols and 4-amido-2H-1-benzopyrans related to the potassium channel activator cromakalim have been prepared and evaluated for their relaxant activity in guinea pig isolated tracheal spirals. Several analogues show enhanced relaxant activity relative to cromakalim in this preparation and the rank order of potency for those substituents investigated at C-6 was CF3 greater than CN greater than C2H5 greater than aza greater than or equal to CH3. One compound, trans-3,4-dihydro-2,2-dimethyl-4-(2-oxopiperidin-1-yl)-7-(trifluor omethyl)-2H- 1-benzopyran-3-ol (24), was resolved into its two enantiomers and the activity was shown to reside essentially in the (+)-isomer, adding further support to the suggestion that the smooth muscle receptor for these potassium channel activators is stereoselective.