2-methyl-6,7-dihydrobenzo[d]oxazol-4(5H)-one | 201024-63-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-methyl-6,7-dihydrobenzo[d]oxazol-4(5H)-one
• 英文别名: 2-Methyl-4,5,6,7-tetrahydro-1,3-benzoxazol-4-one；2-methyl-6,7-dihydro-5H-1,3-benzoxazol-4-one
• CAS: 201024-63-7
• 化学式: C₈H₉NO₂
• 分子量: 151.165
• InChiKey: ICSYEDCLBPZTLC-UHFFFAOYSA-N

物化性质

• 沸点：
  265.7±9.0 °C(Predicted)
• 密度：
  1.208±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  43.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methyl-6,7-dihydrobenzo[d]oxazol-4(5H)-one 在 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 偶氮二异丁腈 、 三氟化硼乙醚 作用下， 以 四氢呋喃 、 四氯化碳 、 正己烷 为溶剂， 反应 1.92h， 生成 2-(bromomethyl)-4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-4,5,6,7-tetrahydro-1,3-benzoxazole
  参考文献：
  名称：

  Structure-Based Design of Potent Retinoid X Receptor α Agonists

  摘要：

  A series of tetrahydrobenzofuranyl and tetrahydrobenzothienyl propenoic acids that showed potent agonist activity against RXRalpha were synthesized via a structure-based design approach. Among the compounds studied, 46a,b showed not only very good potency against RXRalpha (K(i) = 6 nM) but was also found to be greater than 167-fold selective vs RARalpha (K(i) > 1000 nM). This compound profiled out as a full agonist in a cell-based transient transfection assay (EC(50) = 3 nM). The two antipodes were separated via chiral chromatography, and 46b was found to be 40-fold more potent than 46a. Interestingly, cocrystallization of 46a,b with the RXRalpha protein generated a liganded structure whereby the (S)-antipode was found in the binding pocket. Given orally in db/db mice or ZDF rats, 46a,b showed a significant glucose-lowering effect and an increase in liver mass. Triglycerides decreased significantly in db/db mice but increased in the ZDF rats. A dose-dependent decrease of nonesterified free fatty acids was seen in ZDF rats but not in db/db mice. These differences indicate a species specific effect of RXR agonists on lipid metabolism.

  DOI：

  10.1021/jm030565g
• 作为产物：
  描述：

  1,3-环己二酮 在 copper acetylacetonate 、 氢氧化钾 作用下， 以 甲醇 为溶剂， 生成 2-methyl-6,7-dihydrobenzo[d]oxazol-4(5H)-one
  参考文献：
  名称：

  2-苯基碘-1,3-二氧杂环己烷亚甲基的[3 + 2]-环加成反应：熔融二氢呋喃衍生物的简便合成

  摘要：

  衍生自1,3-环己二酮的碘鎓碘化物2与乙腈，二硫化碳和p，p'-二甲氧基硫代二苯甲酮在Cu（acac）2催化下进行热[3 + 2]-环加成反应，形成相应的5元杂环和烯烃分别。光化学反应2与各种烯烃和二烯反应形成二氢呋喃衍生物，这是潘尼硫醚A，B和戊烯合成的关键中间体。

  DOI：

  10.1016/s0040-4039(98)01997-2

文献信息

• SILICON BASED DRUG CONJUGATES AND METHODS OF USING SAME
  申请人：BlinkBio, Inc.

  公开号：US20170202970A1

  公开（公告）日：2017-07-20

  Described herein are silicon based conjugates capable of delivering one or more payload moieties to a target cell or tissue. Contemplated conjugates may include a silicon-heteroatom core, one or more optional catalytic moieties, a targeting moiety that permits accumulation of the conjugate within a target cell or tissue, one or more payload moieties (e.g., a therapeutic agent or imaging agent), and two or more non-interfering moieties covalently bound to the silicon-heteroatom core.

  本文描述了基于硅的共轭物，能够将一个或多个有效载荷基团传递到靶细胞或组织。考虑到的共轭物可能包括一个硅-杂原子核心，一个或多个可选的催化基团，一个定位基团，允许共轭物在靶细胞或组织内积累，一个或多个有效载荷基团（例如，治疗剂或成像剂），以及与硅-杂原子核心共价结合的两个或更多个不干扰基团。
• Synthesis of Highly Substituted Oxazoles through Iodine(III)-Mediated Reactions of Ketones with Nitriles
  作者：Akio Saito、Nao Hyodo、Yuji Hanzawa

  DOI：10.3390/molecules170911046

  日期：——

  trifluoromethanesulfonic acid (TfOH) or bis(trifluoromethane-sulfonyl)imide (Tf2NH), iodosobenzene (PhI=O) efficiently promoted the reactions of dicarbonyl compounds as well as monocarbonyl compounds with nitriles to give 2,4-disubstituted and 2,4,5-trisubstituted oxazole in a single step under the mild conditions.

  在三氟甲磺酸 (TfOH) 或双（三氟甲磺酰基）酰亚胺 (Tf2NH) 存在下，碘代苯 (PhI=O) 有效地促进了二羰基化合物以及单羰基化合物与腈的反应，生成 2,4-二取代和 2 ,4,5-三取代恶唑在温和条件下一步完成。
• [EN] TDO2 INHIBITORS<br/>[FR] INHIBITEURS DE TDO2
  申请人：GENENTECH INC

  公开号：WO2017107979A1

  公开（公告）日：2017-06-29

  Presently provided are inhibitors of cellularly expressed TDO2 and pharmaceutical compositions thereof, useful for modulating an activity of tryptophan 2, 3 dioxygenase; treating immunosuppression; treating a medical conditions that benefit from the inhibition of tryptophan degradation; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; and treating tumor-specific immunosuppression associated with cancer.

  目前提供了细胞表达的TDO2的抑制剂及其药物组合物，用于调节色氨酸2,3双氧酶的活性；治疗免疫抑制；治疗受益于色氨酸降解抑制的医疗状况；增强包括给予抗癌药物在内的抗癌治疗的有效性；以及治疗与癌症相关的肿瘤特异性免疫抑制。
• Synthesis of oxazole and furan derivatives <i>via</i> Rh₂(OAc)₄-catalyzed C≡X bond insertion of cyclic 2-diazo-1,3-diketones with nitriles and arylacetylenes
  作者：Chenli Fan、Xinwei He、Yin Zuo、Yongjia Shang

  DOI：10.1080/00397911.2018.1473441

  日期：2018.11.2

  Abstract A convenient and efficient procedure for the synthesis of 2-substituted-6,7-dihydrobenzo[d]oxazol-4(5H)-ones and 2-aryl-6,7-dihydrobenzofuran-4(5H)-ones through a Rh2(OAc)4-catalyzed C≡X (X = N, C) insertion of cyclic 2-diazo-1,3-diketones with nitriles and aromatic alkynes has been developed. This reaction uses readily available starting materials and stable cyclic 2-diazo-1,3-diketone compounds

  摘要 一种通过 Rh2 合成 2-取代-6,7-二氢苯并[d]恶唑-4(5H)-酮和2-芳基-6,7-二氢苯并呋喃-4(5H)-酮的简便有效方法(OAc)4 催化的 C≡X (X = N, C) 插入环状 2-重氮-1,3-二酮与腈和芳香炔已被开发。该反应使用容易获得的起始材料和稳定的环状 2-重氮-1,3-二酮化合物，以良好至高产率形成所需产物。提出了涉及该反应的 C≡X 键插入和 1,5-偶极电环化/开环和环化序列的初步机制。图形概要
• Selective rxr ligands
  申请人：——

  公开号：US20040198980A1

  公开（公告）日：2004-10-07

  The present invention includes novel retinoid compounds that have selectivity as RXR agonists on one or more isoforms of RXR, currently, RXR&agr;, RXR&bgr;, or RXR&ggr;. The present compounds, and pharmaceutical compositions incorporating these compounds, therefore, are effective in treating conditions mediated by RXRs. Among other physiological responses, the compounds of the present invention reduce blood glucose and maintain body weight, and, thus, are useful for the treatment of diabetes (NIDDIM) and obesity.

  本发明涵盖了新型视黄醇化合物，其在RXR的一个或多个亚型上具有选择性作为RXR激动剂，目前包括RXRα、RXRβ或RXRγ。因此，本化合物及包含这些化合物的药物组合物在治疗由RXR介导的疾病方面是有效的。除其他生理反应外，本发明的化合物可降低血糖并维持体重，因此对于治疗糖尿病（NIDDIM）和肥胖症是有用的。