4,4-二甲基苯并二氢吡喃-6-羧酸 | 104224-91-1

• 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: 4,4-二甲基苯并二氢吡喃-6-羧酸
• 英文名称: 4,4-dimethylchroman-6-carboxylic acid
• 英文别名: 4,4-dimethyl-2,3-dihydro-1-benzopyran-6-carboxylic acid；4,4-dimethyl-6-carboxy chroman；4,4-Dimethyl-3,4-dihydro-2H-1-benzopyran-6-carboxylic acid；4,4-dimethyl-2,3-dihydrochromene-6-carboxylic acid
• CAS: 104224-91-1
• 化学式: C₁₂H₁₄O₃
• 分子量: 206.241
• InChiKey: CVBFKXGFMBOPIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,4-二甲基苯并二氢吡喃-6-羧酸 在 氯化亚砜 作用下， 反应 16.0h， 生成 4,4-dimethyl-2,2-dihydro-1-benzopyran-6-carboxylic acid chloride
  参考文献：
  名称：

  Heteroarotinoids Inhibit Head and Neck Cancer Cell Lines in Vitro and in Vivo Through Both RAR and RXR Retinoic Acid Receptors

  摘要：

  A class of less toxic retinoids, called heteroarotinoids, was evaluated for their molecular mechanism of growth inhibition of two head and neck squamous cell carcinoma (HNSCC) cell lines SCC-2 and SCC-38. A series of 14 heteroarotinoids were screened for growth inhibition activity in vitro. The two most active compounds, one that contained an oxygen heteroatom (6) and the other a sulfur heteroatom (16), were evaluated in a xenograph model of tumor establishment in nude mice. Five days after subcutaneous injection of 10(7) SCC-38 cells, groups of 5 nu / nu mice were gavaged daily (5 days/week for 4 weeks) with 20 mg/kg/day of all-trans-retinoic acid (t-RA, 1), 10 mg/kg/day of 6, 10 mg/kg/day of 16, or sesame oil. After a few days, the dose of t-RA (1) was decreased to 10 mg/kg/day to alleviate the side effects of eczema and bone fracture. No significant toxic effects were observed in the heteroarotinoid groups. All three retinoids caused a statistically significant reduction in tumor size as determined by the Student t-test (P < 0.05). Complete tumor regression was noted in 3 of 5 mice treated with t-RA (1), 4 of 5 mice treated with 16, 1 of 5 mice treated with 6, and 1 of 5 mice treated with sesame oil. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine that the expression levels of RAR alpha, RXR alpha, and RXR beta were similar in the two cell lines, while RAR beta expression was higher in SCC-2 over SCC-38, and RAR gamma expression was higher in SCC-38 over SCC-2. Receptor cotransfection assays in CV-1 cells demonstrated that 16 was a potent activator of both RAR and RXR receptors, while 6 was selective for the RXR receptors. Transient cotransfection assays in CV-1 cells using an AP-1 responsive reporter plasmid demonstrated that t-RA (1), 6, and 16 each inhibited AP-1-driven transcription in this cell line. In conclusion, the growth inhibition activity of the RXR-selective 6 and the more potent growth inhibition activity of the RAR/RXR pan-agonist 16 implicate both RARs and RXRs in the molecular mechanism of retinoid growth inhibition. Moreover, the chemoprevention activity and the lack of toxicity of heteroarotinoids demonstrate their clinical potential in head and neck cancer chemoprevention.

  DOI：

  10.1021/jm990292i
• 作为产物：
  描述：

  ethyl 4,4-dimethylchroman-6-carboxylate 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 以89%的产率得到4,4-二甲基苯并二氢吡喃-6-羧酸
  参考文献：
  名称：

  1,3,3-三甲基吲哚-5-胺和4-甲酰基4,4-二甲基苯并-6-羧酸盐硫杂氨基甲酸酯（OHet72）

  摘要：

  （2021年）。1,3,3-Trimethylindolin-5-amine和4-formylphenyl 4,4-Dimethylchroman-6-carboxylate Thiosemicarbazone（OHet72）有机制备和程序，国际：53，第1页，第68-77页。

  DOI：

  10.1080/00304948.2020.1834819

文献信息

• Synthesis of Potential Metabolites of Ethyl (E)-4-[2-(3,4-Dihydro-4,4-dimethyl-2H-1-benzopyran-6-yl)-1-propenyl]benzoate
  作者：P.S. Sunthankar、K.D. Berlin、Eldon C. Nelson、R. Lori Thorne、Paul W. Geno、Jeffrey C. Archer、Lester L. Rolf、Kenneth E. Bartels

  DOI：10.1002/jps.2600820522

  日期：1993.5

  2-butenolide, ethyl (E)-4-[3,4-dihydro-4,4-dimethyl-2H-1-benzopyran-6-yl)-3-hydroxy-1- propenyl]benzoate, ethyl (E)-4-[2-(3,4-dihydro-4,4-dimethyl-2H-1-benzopyran-6-yl)-2-propenal] benzoate, and ethyl (E)-4-[2-(3,4-dihydro-4,4-dimethyl-2H-1-benzopyran-6-yl)-2-propenoic+ ++ acid]benzoate. Stereospecific oxidizing reagents and/or conditions were developed for these sensitive systems and include the use

  合成了（E）-4- [2-（3,4-二氢-4,4-二甲基-2H-1-苯并吡喃-6-基）-1-丙烯基]苯甲酸乙酯的潜在代谢产物。新化合物包括3- [3,4-二氢-4,4-二甲基-2H-1-苯并吡喃-6-基]巴豆酸酯，3- [3,4-二氢-4,4-二甲基-1H-1 -苯并吡喃-6-基]巴豆酸，3,4-二氢-4,4-二甲基-2H-1-苯并吡喃-6-羧酸，4- [3,4-二氢-4,4-二甲基-2H- 1-苯并吡喃-6-基]δ2-丁烯内酯，乙基（E）-4- [3,4-二氢-4,4-二甲基-2H-1-苯并吡喃-6-基）-3-羟基-1-丙烯基]苯甲酸酯，（E）-4- [2-（3,4-二氢-4,4-二甲基-2H-1-苯并吡喃-6-基）-2-丙烯基]苯甲酸乙酯和（E）-乙基4- [2-（3,4-二氢-4,4-二甲基-2H-1-苯并吡喃-6-基）-2-丙烯酸+++酸]苯甲酸酯。针对这些敏感系统开发了立体特异性
• Aryl or heteroaryl amides of tetrahydronaphthalene, chroman, thichroman and 1,2,3,4-tetrahydroquinolinecarboxlic acids, having an electron withdrawing substituent in the aromatic or heteroaromatic moiety, having retinoid-like biological activity
  申请人：Allergan Sales, Inc.

  公开号：US06342602B1

  公开（公告）日：2002-01-29

  Compounds of the formula wherein the symbols have the meaning defined in the specification have retinoid-like biological activity.

  该式化合物具有类视黄醇生物活性，其中符号的含义在规范中定义。
• Chroman esters of phenols and benzoic acids having retinoid-like activity
  申请人：Allergan, Inc.

  公开号：US05006550A1

  公开（公告）日：1991-04-09

  Retinoid like activity is exhibited by compounds of the formula ##STR1## wherein the R.sub.1 -R.sub.7 groups are independently H or straight chain or branched chain lower alkyl or cycloalkyl of 1 to 6 carbons; X symbolizes an ester or thioester linkage, Y is cycloalkyl or branched chain alkyl of 1 to 6 carbons or is (CH.sub.2) where n is an integer between 0 to 6 or is an alkenyl group of 2 to 6 carbons, or an alkynyl group of 2 to 6 carbons; and Z is H, OH, OR', OCOR', --COOH or a pharmaceutically acceptable salt, ester or amide thereof, --CH.sub.2 OH or an ether or ester derivative, or --CHO or an acetal derivative, or --COR' or a ketal derivative where R' is an alkyl, cycloalkyl or alkenyl group containing 1 to 6 carbons, or a phenylalkyl, phenyl or substituted phenyl group.

  化合物的式子为 ##STR1## 其中 R.sub.1 -R.sub.7 基团独立地为 H 或直链或支链低碳数烷基或环烷基；X 代表酯或硫酯键，Y 为1至6个碳的支链烷基或环烷基或为(CH.sub.2)，其中n为0至6的整数，或为2至6个碳的烯基基团或2至6个碳的炔基基团；Z 为H、OH、OR'、OCOR'、--COOH 或其药学上可接受的盐、酯或酰胺、--CH.sub.2 OH 或其醚或酯衍生物、--CHO 或其缩醛衍生物、--COR' 或其缩酮衍生物，其中R'是含1至6个碳的烷基、环烷基或烯基基团或苯基烷基、苯基或取代苯基。
• Methods of treatment with compounds having RAR alpha receptor specific or selective activity
  申请人：Allergan Sales, Inc.

  公开号：US20020077360A1

  公开（公告）日：2002-06-20

  Retinoid compounds which act specifically or selectively on RAR &agr; receptor subtypes in preference over RAR &bgr; and RAR &Ggr; receptor subtypes, posses desirable pharmaceutical properties associated with retinoids, and are particularly suitable for treatment of tumors, such as acute monocytic leukemia, cervical carcinoma, myeloma, ovarian carcinomas and head and neck carcinomas, without having one or more undesirable side effects of retinoids, such as inducement of weight loss, mucocutaneous toxicity, skin irritation and teratogenecity.

  作用于RARα亚型的视黄酸类化合物，具有优于RARβ和RARγ亚型的选择性或特异性，具有与视黄酸相关的理想药物特性，特别适用于治疗肿瘤，如急性单核细胞白血病、宫颈癌、骨髓瘤、卵巢癌和头颈癌，而不具有视黄酸的一个或多个不良副作用，如诱导体重减轻、粘膜皮肤毒性、皮肤刺激和致畸性。
• Heterocyclic GPR40 Modulators
  申请人：Beck Hilary

  公开号：US20080090840A1

  公开（公告）日：2008-04-17

  The present invention provides compounds useful, for example, for treating metabolic disorders in a subject. Such compounds have the general formula I: where the definitions of the variables are provided herein. The present invention also provides compositions that include, and methods for using, the compounds in preparing medicaments and for treating metabolic disorders such as, for example, type II diabetes.

  本发明提供了一些化合物，例如用于治疗受试者的代谢紊乱。此类化合物具有一般式I，其中变量的定义在此提供。本发明还提供了包含这些化合物的组合物以及使用这些化合物制备药物和治疗代谢紊乱（例如II型糖尿病）的方法。