5-isopropyl-3-isoxazolol | 10004-47-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-isopropyl-3-isoxazolol
• 英文别名: 5-isopropylisoxazol-3-ol；5-isopropyl-isoxazol-3-one；5-propan-2-yl-1,2-oxazol-3-one
• CAS: 10004-47-4
• 化学式: C₆H₉NO₂
• 分子量: 127.143
• InChiKey: WKKVFNUVMXLZDZ-UHFFFAOYSA-N

物化性质

• 熔点：
  41-42 °C
• 密度：
  1.099±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-isopropyl-3-isoxazolol 在 氢溴酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 18.0h， 生成 4-(Bromomethyl)-2-(methoxymethyl)-5-propan-2-yl-1,2-oxazol-3-one
  参考文献：
  名称：

  Excitatory amino-acid receptor agonists. Synthesis and pharmacology of analogues of 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid

  摘要：

  We have previously proposed the existence of a lipophilic cavity of the 2-amino-3-(3-hydroxy-5-methylisoxazol4-yl)propionic acid (AMPA) receptor recognition site capable of accommodating alkyl substituents of limited size in the 5-position of the isoxazole ring. In order to indirectly elucidate the approximate extent of this proposed cavity we have synthesized and pharmacologically characterized a number of AMPA analogues. For most of these AMPA analogues, a positive correlation between AMPA receptor affinity and agonist effect was observed. The only exception was demethyl-AMPA (8a), which showed relatively high AMPA receptor affinity (IC50 = 0.27 mu M) but remarkably weak agonist potency (EC50 = 900 mu M). Whereas the ethyl analogue of AMPA (Et-AMPA) (IC50 = 0.030 mu M; EC50 = 2.3 mu M) has previously been shown to be slightly more potent than AMPA (IC50 = 0.040 mu M; EC50 = 3.5 mu M), substitutions of a propyl or a butyl group for the methyl group of AMPA to give 8b (IC50 = 0.090 mu M; EC50 = 5.0 mu M) or 8f (IC50 = 1.0 mu M; EC50 = 32 mu M), respectively, result in progressive loss of the AMPA agonist effect. Analogues containing larger groups, such as isopentyl (8e), 1-propylbutyl (8g), 2,2-dimethylpropyl (8h), or benzyl (14) groups, were very weak or totally inactive as AMPA receptor ligands.

  DOI：

  10.1016/s0223-5234(97)89085-x
• 作为产物：
  描述：

  异丁酰基米氏酸 在 盐酸 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 16.0h， 生成 5-isopropyl-3-isoxazolol
  参考文献：
  名称：

  5-取代的3-异恶唑醇的新颖途径。通过酰基麦德鲁姆酸合成的N，O-DiBocβ-酮异羟肟酸的环化反应。

  摘要：

  3-异恶唑醇最通常由β-酮酯和羟胺合成。该环化通常产生主要副产物，相应的5-异恶唑酮。我们已经发现，可以合成N，O-diBoc保护的β-酮异羟肟酸并将其环化成5-取代的3-异恶唑醇，而不会形成任何副产物。我们提出了一种新颖且通用的三步程序，其中将羧酸衍生物转化为酰基麦德鲁姆酸，当与N，O-双（叔丁氧基羰基）羟胺进行氨解后，会生成N，O-diBoc保护的β-酮异羟肟酸。然后，将这些异羟肟酸类似物用盐酸处理后，环化成相应的5-取代的3-异恶唑醇。

  DOI：

  10.1021/jo991409d

文献信息

• Benzoxazinyl-amidocyclopentyl-heterocyclic modulators of chemokine receptors
  申请人：Goble D. Stephen

  公开号：US20070238723A1

  公开（公告）日：2007-10-11

  Cyclopentyl compounds linked to a benzoxazinyl group through an amido moiety utilizing the ring nitrogen of the benzoxazine, and further substituted with a heterocyclic moiety, such compounds represented by formula I: which are used to modulate the CCR-2 chemokine receptor to prevent or treat inflammatory and immunoregulatory disorders and diseases, allergic diseases, atopic conditions including allergic rhinitis, dermatitis, conjunctivitis, and asthma, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis; and pharmaceutical compositions comprising these compounds and the use of these compounds and compositions.

  环戊基化合物通过酰胺基团与苯并噁唑基团相连，利用苯并噁唑环的环氮原子，并进一步用杂环基团取代，这些化合物由式I表示： 用于调节CCR-2趋化因子受体，以预防或治疗炎症和免疫调节性疾病和疾病，过敏性疾病，包括过敏性鼻炎，皮炎，结膜炎和哮喘，以及类风湿性关节炎和动脉粥样硬化等自身免疫病理病变；以及包含这些化合物的药物组合物和这些化合物和组合物的使用。
• THERAPEUTIC COMPOUNDS
  申请人：CELGENE QUANTICEL RESEARCH, INC.

  公开号：US20170298040A1

  公开（公告）日：2017-10-19

  The present disclosure relates to substituted heterocyclic derivative therapeutic compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of diseases mediated by aberrant cell signalling, such as inflammatory disorders, cancer and neoplastic disease.

  本公开涉及替代杂环衍生治疗化合物，包括所述化合物的组合物，以及通过抑制溴结构域介导的乙酰赖氨酸区域对蛋白质（如组蛋白）的识别来进行表观遗传调控的所述化合物和组合物的用途。所述组合物和方法对于治疗由异常细胞信号传导介导的疾病，如炎症性疾病、癌症和肿瘤性疾病，是有用的。
• SOLUBLE GUANYLATE CYCLASE STIMULATORS
  申请人：Berger Raphaelle

  公开号：US20170174693A1

  公开（公告）日：2017-06-22

  The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R 1 , R 2 , R 4 , R a , and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate (“cGMP”), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose.

  该发明提供了Formula (I)的化合物或其药用盐，其中X、Y、Z、R1、R2、R4、Ra以及下标m、p和q如本文所述。这些化合物或其药用盐可以调节人体对环鸟苷酸单磷酸（“cGMP”）的产生，并通常适用于治疗和预防与扰乱的cGMP平衡相关的疾病。该发明还提供了包含Formula (I)的化合物或其药用盐的药物组合物。该发明还涉及使用这些化合物或其药用盐在治疗和预防上述疾病以及为此目的制备药物的方法。
• Substituted Pyrrolidines and Methods of Use
  申请人：AbbVie S.à.r.l.

  公开号：US20180099931A1

  公开（公告）日：2018-04-12

  The invention discloses compounds of Formula (I) wherein R 1 , R 2 , R 2A , R 3 , R 3A , R 4 , R 4A , and R 5 are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

  该发明公开了式（I）的化合物 其中R 1 ，R 2 ，R 2A ，R 3 ，R 3A ，R 4 ，R 4A 和R 5 如本文所定义。本发明涉及化合物及其在囊性纤维化治疗中的应用，其生产方法，包含相同化合物的药物组合物，以及通过给予该发明的化合物来治疗囊性纤维化的方法。
• HISTONE DEMETHYLASE INHIBITORS
  申请人：Quanticel Pharmaceuticals, Inc.

  公开号：US20140171432A1

  公开（公告）日：2014-06-19

  The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted 3-aminopyridine derivative compounds, substituted 3-aminopyridazine derivative compounds, and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

  本发明一般涉及治疗癌症和肿瘤性疾病的组合物和方法。本文提供了替代的3-氨基吡啶衍生物化合物，替代的3-氨基吡啶嗪衍生物化合物，以及包含所述化合物的药物组合物。所述化合物和组合物对于抑制组蛋白去甲基化酶是有用的。此外，所述化合物和组合物对于治疗癌症，如前列腺癌、乳腺癌、膀胱癌、肺癌和/或黑色素瘤等是有用的。