2,2-二甲基色烯-6-羧酸 | 34818-56-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 2,2-二甲基色烯-6-羧酸
• 英文名称: anofinic acid
• 英文别名: 2,2-dimethyl-2H-chromene-6-carboxylic acid；2,2-dimethyl-2H-1-benzopyran-6-carboxylic acid；2,2-dimethyl-2H-1-chromene-6-carboxylic acid；2,2-dimethylchromene-6-carboxylic acid
• CAS: 34818-56-9
• 化学式: C₁₂H₁₂O₃
• mdl: MFCD06208181
• 分子量: 204.225
• InChiKey: AXICIBPYBONRSP-UHFFFAOYSA-N

物化性质

• 物理描述：
  Solid
• 熔点：
  160°C

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2916190090

反应信息

• 作为反应物：
  描述：

  2,2-二甲基色烯-6-羧酸 在 草酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 2,2-dimethyl-N-phenyl-2H-1-benzopyran-6-carboxamide
  参考文献：
  名称：

  Cardioselective Antiischemic ATP-Sensitive Potassium Channel (K_ATP) Openers. 6. Effect of Modifications at C6 of Benzopyranyl Cyanoguanidines

  摘要：

  The effect on potency and selectivity of modifications at the C6 position of the cardioprotective K-ATP Opener BMS-180448 (2) is described. Structure-activity studies show that a variety of electron-withdrawing groups (ketone, sulfone, sulfonamide, etc.) are tolerated for cardioprotective activity as measured by EC25 values for an increase in time to the onset of contracture in globally ischemic rat, hearts. Changes made to the sulfonamido substituent indicate that compounds derived from secondary lipophilic amines are preferred for good cardioprotective potency and selectivity. The diisobutyl analogue 27 (EC25 = 0.04 mu M) is the most potent compound of this series. The cardiac selectivity of 27 results from a combination of reduced vasorelaxant potency and enhanced cardioprotective potency relative to the potent vasodilating K-ATP openers (e.g., cromakalim). The diisobutylsulfonamide analogue 27 is over 4 orders of magnitude more cardiac selective than cromakalim (1), These results support the hypothesis that the cardioprotective and vasorelaxant properties of K-ATP openers follow distinct structure-activity relationships. The mechanism of action of 27 appears to involve opening of the cardiac K-ATP as its cardioprotective effects are abolished by the K-ATP blocker glyburide.

  DOI：

  10.1021/jm990196h
• 作为产物：
  描述：

  methyl 2,2-dimethyl-2H-1-benzopyran-6-carboxylate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 4.5h， 以87%的产率得到2,2-二甲基色烯-6-羧酸
  参考文献：
  名称：

  Synthesis and Structure−Phytotoxicity Relationships of Acetylenic Phenols and Chromene Metabolites, and Their Analogues, from the Grapevine Pathogen Eutypa lata

  摘要：

  Eutypa lata, the fungus responsible for dying-arm disease in grapevines, produces a number of structurally related secondary metabolites, of which eutypine (1) has been implicated as the principal phytotoxin. However, analysis of an E. lata strain from California known to be pathogenic to grapevines showed that eutypine was not present, suggesting that other metabolites could be phytotoxic. Investigation of the relative phytotoxicities of individual metabolites has been limited by insufficient material and lack of a reliable bioassay. Metabolites of particular interest and their precursors were therefore synthesized, and a rapid, quantitative bioassay via topical application of individual compounds to disks of grape leaves and measurement of chlorophyll loss was developed to provide a relative measure of tissue damage. The recently reported metabolite eulatachromene (2) was found to have phytotoxicity greater than that of eutypine (1). The cyclization product, 5-formyl-2-methylvinyl[1]benzofuran (3), also showed significant activity, whereas the reduction product, eutypinol (4), was inactive, as was the quinol, siccayne (5). These results indicate that before strains of Eutypa are incriminated as pathogenic they must be analyzed for the presence or absence of specific constituents for which the phytotoxicity has been unequivocally established.

  DOI：

  10.1021/np020415t

文献信息

• Benzopyranes as potassium channel openers
  申请人：Pfizer Inc.

  公开号：US05677324A1

  公开（公告）日：1997-10-14

  The present invention relates to compounds of formula (I) and the pharmaceutically acceptable salts thereof, wherein the dashed line represents an optional covalent bond; X is O, NH, S or a direct link; R.sup.3 is hydroxy when the dashed line does not represent a covalent bond and R.sup.3 is absent when the dashed line represents a covalent bond; R.sup.4 is (a), when X is O, a group of formula (i), (b), when X is O, NH or S, optionally substituted hydroxyphenyl, (c) an optionally substituted 4- to 7-membered heterocyclic ring, or (d), when X is NH, a group of formula (ii). The compounds are useful for the treatment of disease associated with the altered tone or motility of smooth muscle. ##STR1##

  本发明涉及式(I)的化合物及其药学上可接受的盐，其中虚线代表可选的共价键；X为O、NH、S或直接连接；当虚线不代表共价键时，R.sup.3为羟基，当虚线代表共价键时，R.sup.3不存在；当X为O时，R.sup.4为(a)，为式(i)的基团，当X为O、NH或S时，为可选取代的羟基苯基(b)，为可选取代的4-至7-成员杂环环(c)，或当X为NH时，为式(ii)的基团(d)。这些化合物对于治疗与平滑肌张力或运动异常相关的疾病是有用的。
• Natural Product-like Combinatorial Libraries Based on Privileged Structures. 1. General Principles and Solid-Phase Synthesis of Benzopyrans
  作者：K. C. Nicolaou、J. A. Pfefferkorn、A. J. Roecker、G.-Q. Cao、S. Barluenga、H. J. Mitchell

  DOI：10.1021/ja002033k

  日期：2000.10.1

  report a novel strategy for the design and construction of natural and natural product-like libraries based on the principle of privileged structures, a term originally introduced to describe structural motifs capable of interacting with a variety of unrelated molecular targets. The identification of such privileged structures in natural products is discussed, and subsequently the 2,2-dimethylbenzopyran

  在此，我们报告了一种基于特权结构原理设计和构建天然和天然产物类库的新策略，该术语最初用于描述能够与各种不相关的分子靶标相互作用的结构基序。讨论了天然产物中此类特权结构的鉴定，随后选择 2,2-二甲基苯并吡喃部分作为通过该策略构建类天然产物库的初始模板。最初，采用独特的环加载策略开发了苯并吡喃基序的新型固相合成，该策略依赖于使用新的聚苯乙烯基溴化硒树脂。一旦确定了这些苯并吡喃的加载、加工和裂解，
• Discovery and Biological Activity of 6BrCaQ as an Inhibitor of the Hsp90 Protein Folding Machinery
  作者：Davide Audisio、Samir Messaoudi、Lukasz Cegielkowski、Jean-François Peyrat、Jean-Daniel Brion、Délphine Methy-Gonnot、Christine Radanyi、Jack-Michel Renoir、Mouâd Alami

  DOI：10.1002/cmdc.201000489

  日期：2011.5.2

  the simplified 3‐aminoquinolein‐2‐one analogue 2 b (6BrCaQ), which manifests micromolar activity against a panel of cancer cell lines. The molecular signature of Hsp90 inhibition was assessed by depletion of standard known Hsp90 client proteins. Finally, processing and activation of caspases 7, 8, and 9, and the subsequent cleavage of PARP by 6BrCaQ, suggest stimulation of apoptosis through both extrinsic

  热休克蛋白90（Hsp90）由于其在与细胞增殖和生存能力相关的多种信号通路的十字路口的作用而成为合理癌症治疗发展中的重要目标。在这里，合成了一系列新型的Hsp90抑制剂，其中含有一个quinolein-2-one支架，并在细胞增殖试验中进行了评估。这些结构-活性关系研究的结果使鉴定简化的3-氨基喹诺酮-2-酮类似物2 b成为可能。（6BrCaQ），对一组癌细胞系表现出微摩尔活性。Hsp90抑制的分子特征是通过消耗已知的标准Hsp90客户蛋白质来评估的。最后，胱天蛋白酶7、8和9的加工和激活以及随后的6BrCaQ对PARP的切割，提示通过外在和内在途径刺激凋亡。
• Synthesis and biological activity of simplified denoviose-coumarins related to novobiocin as potent inhibitors of heat-shock protein 90 (hsp90)
  作者：Christine Radanyi、Gaëlle Le Bras、Samir Messaoudi、Céline Bouclier、Jean-François Peyrat、Jean-Daniel Brion、Véronique Marsaud、Jack-Michel Renoir、Mouâd Alami

  DOI：10.1016/j.bmcl.2008.01.128

  日期：2008.4

  A new series of coumarin inhibitors of hsp90 lacking the noviose moiety as well as substituents on C-7 and C-8 positions of the aromatic ring was synthesised and their hsp90 inhibitory activity has been delineated: for example, their capacity to induce the degradation of client proteins and to inhibit estradiol-induced transcription in human breast cancer cells. In cell proliferation assay, the most

  合成了一系列新的hsp90香豆素抑制剂，它们缺少新手部分以及芳香环的C-7和C-8位置上的取代基，并且已经描述了它们的hsp90抑制活性：例如，它们诱导Hsp90降解的能力。客体蛋白并抑制雌二醇诱导的人乳腺癌细胞转录。在细胞增殖试验中，活性最高的化合物5g的效价约为其母体新霉素天然化合物的8倍。
• Acylations of 2,2-Dimethyl-2<i>H</i>-chromenes
  作者：Seiji Yamaguchi、Satoru Yamamoto、Shoichi Abe、Yoshiyuki Kawase

  DOI：10.1246/bcsj.57.442

  日期：1984.2

  Orientation in acylation reactions of 2,2-dimethyl-2H-chromenes was studied. Five acetylchromenes were obtained with two methods and six formylchromenes were obtained with a third method. Demethylation of four acyl-methoxy-substituted chromenes gave the corresponding acylchromenols. 2,2-Dimethyl-2H-chromene-6-carboxylic acid (anofinic acid) was also obtained by oxidation of 6-formylchromene.

  研究了 2,2-二甲基-2H-苯酰化反应中的定向。通过两种方法得到了五个乙酰基苯并通过第三种方法得到了六个甲酰基苯并。四种酰基甲氧基取代色烯的脱甲基反应得到了相应的酰基色酚。通过 6-甲酰基色烯的氧化作用，还得到了 2,2-二甲基-2H-色烯-6-羧酸（anofinic acid）。