甲基5-(羟基甲基)-1,2-恶唑-3-羧酸酯 | 139297-55-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 甲基5-(羟基甲基)-1,2-恶唑-3-羧酸酯
• 中文别名: 5-(羟甲基)异恶唑-3-甲酸甲酯；3-异恶唑甲酸-5-(羟甲基)-甲基酯(9CI)
• 英文名称: methyl 5-(hydroxymethyl)isoxazole-3-carboxylate
• 英文别名: Methyl 5-(hydroxymethyl)-1,2-oxazole-3-carboxylate
• CAS: 139297-55-5
• 化学式: C₆H₇NO₄
• mdl: MFCD14706527
• 分子量: 157.126
• InChiKey: XUDZZTFUHHYXSE-UHFFFAOYSA-N

物化性质

• 沸点：
  333.9±32.0 °C(Predicted)
• 密度：
  1.341±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	methyl 5-(tetrahydro-2H-pyran-2-yloxymethyl)isoxazole-3-carboxylate	252769-66-7	C11H15NO5	241.244

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  5-羟基甲基异噁唑-3-羧酸	5-(hydroxymethyl)isoxazole-3-carboxylic acid	139297-56-6	C5H5NO4	143.099
  5-甲酰基异恶唑-3-甲酸甲酯	methyl 5-formylisoxazole-3-carboxylate	22667-21-6	C6H5NO4	155.11
  ——	5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)isoxazole-3-carboxylic acid	215872-14-3	C10H13NO5	227.217

反应信息

• 作为反应物：
  描述：

  甲基5-(羟基甲基)-1,2-恶唑-3-羧酸酯 在 lithium hydroxide 、 potassium tert-butylate 、 水 、 pyridinium chlorochromate 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 31.0h， 生成 5-[(E)-2-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-propenyl]-isoxazole-3-carboxylic acid
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Novel Heteroretinoids:  Induction of Apoptosis in the HL-60 Cell Line by a Novel Isoxazole-Containing Heteroretinoid

  摘要：

  In a search for retinoic acid receptor (RAR and RXR)-selective ligands, a series of isoxazole retinoids was synthesized and evaluated in vitro in transcriptional activation and competition binding assays for RARs and RXRs. In addition, these compounds were evaluated for their differentiating, cytotoxic, and apoptotic activities. In general, these derivatives showed scarcely any binding affinity and were nest active in the transcriptional assay. However, among these isoxazole derivatives, the cis-isomer 14b was identified as a potent inducer of apoptosis, and its activity was found to be 6.5 and 4 times superior than that of 13-cis- and 9-cis-retinoic acids, respectively. On the other hand, compound 13b, which has the trans stereochemistry at the double bond, was found not to be active in the apoptotic assay, but it was endowed with appreciable differentiating activity. Therefore, it seems that the different stereochemistry of the double bond may be associated with a different biological activity: potent apoptotic activity for the cis-isomer but differentiating activity for the traits structure. This biological behavior was found, at least in part, for the 9-cis- and 13-cis-retinoic acids with respect to the all-trans-retinoic acid. Thus, structure 14b could offer an interesting model for the design of new compounds endowed with apoptotic activity.

  DOI：

  10.1021/jm991059n
• 作为产物：
  描述：

  methyl 5-(tetrahydro-2H-pyran-2-yloxymethyl)isoxazole-3-carboxylate 在 Amberlite H-15 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以88%的产率得到甲基5-(羟基甲基)-1,2-恶唑-3-羧酸酯
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Novel Heteroretinoids:  Induction of Apoptosis in the HL-60 Cell Line by a Novel Isoxazole-Containing Heteroretinoid

  摘要：

  In a search for retinoic acid receptor (RAR and RXR)-selective ligands, a series of isoxazole retinoids was synthesized and evaluated in vitro in transcriptional activation and competition binding assays for RARs and RXRs. In addition, these compounds were evaluated for their differentiating, cytotoxic, and apoptotic activities. In general, these derivatives showed scarcely any binding affinity and were nest active in the transcriptional assay. However, among these isoxazole derivatives, the cis-isomer 14b was identified as a potent inducer of apoptosis, and its activity was found to be 6.5 and 4 times superior than that of 13-cis- and 9-cis-retinoic acids, respectively. On the other hand, compound 13b, which has the trans stereochemistry at the double bond, was found not to be active in the apoptotic assay, but it was endowed with appreciable differentiating activity. Therefore, it seems that the different stereochemistry of the double bond may be associated with a different biological activity: potent apoptotic activity for the cis-isomer but differentiating activity for the traits structure. This biological behavior was found, at least in part, for the 9-cis- and 13-cis-retinoic acids with respect to the all-trans-retinoic acid. Thus, structure 14b could offer an interesting model for the design of new compounds endowed with apoptotic activity.

  DOI：

  10.1021/jm991059n

文献信息

• Mechanochemistry Enabled Construction of Isoxazole Skeleton <i>via</i> CuO Nanoparticles Catalyzed Intermolecular Dehydrohalogenative Annulation
  作者：Murugan Vadivelu、Sugirdha Sampath、Kesavan Muthu、Kesavan Karthikeyan、Chandrasekar Praveen

  DOI：10.1002/adsc.202100730

  日期：2021.11.9

  accomplished. This chemistry is operative under the cooperative catalysis of cupric oxide nanoparticles (<50 nm) and DABCO. The key beneficial aspects of this protocol include: (i) broad substrate scope, (ii) no vigorous work-up, (iii) short reaction time, (iv) solvent-free condition, (v) commercial viability of substrates/reagents (vi) good chemical yields and selectivity. The other merit of this chemistry

  通过在机械化学设置下将β-乙烯基卤化物和α-硝基羰基化合物配对，完成了异恶唑环化的脱卤化氢方法。这种化学反应在氧化铜纳米粒子 (<50 nm) 和 DABCO 的协同催化下起作用。该协议的主要有益方面包括：（i）广泛的底物范围，（ii）没有剧烈的后处理，（iii）反应时间短，（iv）无溶剂条件，（v）底物/试剂的商业可行性（ vi) 良好的化学产率和选择性。这种化学反应的另一个优点是反应后 CuO 可以很容易地回收和再利用，六次运行的催化活性没有太大的下降。由于不受 β-乙烯基卤化物的限制，验证条件也对炔烃开放，用于制备异恶唑，
• [EN] PHTHALAZINE DERIVATIVES, AND PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF<br/>[FR] DÉRIVÉ DE PHTHALAZINE ET PROCÉDÉ DE PRÉPARATION, COMPOSITION PHARMACEUTIQUE ET UTILISATION ASSOCIÉES<br/>[ZH] 呔嗪类衍生物、其制备方法、药物组合物和用途
  申请人：SHANGHAI SIMR BIOTECH CO LTD

  公开号：WO2017097217A1

  公开（公告）日：2017-06-15

  本发明提供一种通式（I）所示的化合物、其顺反异构体、对映异构体、非对映异构体、外消旋体、溶剂合物、水合物、或其药学上可以接受的盐和酯，其制备方法，含有该化合物的药物组合物以及所述化合物作为α5‐GABAA受体调节剂的用途，其中T、Z、A、Y如说明书中所定义。
• New N-aryl isoxazolecarboxamides and N-isoxazolylbenzamides as anticonvulsant agents
  作者：F Lepage、F Tombret、G Cuvier、A Marivain、JM Gillardin

  DOI：10.1016/0223-5234(92)90137-p

  日期：1992.9

  We prepared a series of N-aryl isoxazolecarboxamide, N-isoxazolylbenzamide compounds and derivatives and studied their anticonvulsant action in MES and MMS tests. Some of these reveal considerable activity, especially with respect to MES test. The disubstitution in the 2.6-position on the phenyl ring by two methyl groups would appear to be of primary importance for the activity. The amide bridge between the phenyl and isoxazolic rings, whether of the anilide or benzamide type, seems to show similar anticonvulsant behavior. We have selected the derivatives 8 (N-(2.6-dimethylphenyl)-5-methyl-3-isoxazolecarboxamide, 12 (N-(2,6-dimethylphenyl)-5-hydroxymethyl-3-isoxazolecarboxamide) and 51 (N-(5-methyl-3-isoxazolyl)-2.6-dimethylbenzamide) which are presently being studied in more extended pharmacological tests.
• Substituted Tetrahydropyrrolo[2,1-<i>b</i>]oxazol-5(6<i>H</i>)-ones and Tetrahydropyrrolo[2,1-<i>b</i>]thiazol-5(6<i>H</i>)-ones as Hypoglycemic Agents
  作者：Thomas D. Aicher、Bork Balkan、Philip A. Bell、Leonard J. Brand、S. H. Cheon、Rhonda O. Deems、Jay B. Fell、William S. Fillers、James D. Fraser、Jiaping Gao、Douglas C. Knorr、Gerald G. Kahle、Christina L. Leone、Jeffrey Nadelson、Ronald Simpson、Howard C. Smith

  DOI：10.1021/jm9803121

  日期：1998.11.1

  A series of substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-one and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones was synthesized from amino alcohols or amino thiols and keto acids. A pharmacological model based on the results obtained with these compounds led to the synthesis and evaluation of a series of isoxazoles and other monocyclic compounds. These were evaluated for their ability to enhance glucose utilization in cultured L6 myocytes. The in vivo hypoglycemic efficacy and potency of these compounds were evaluated in a model of type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus), the ob/ob mouse. 25a(2S) (SDZ PGU 693) was selected for further pharmacological studies.
• EP3388433
  申请人：——

  公开号：——

  公开（公告）日：——