t-Butylmalonsaeuremonobenzylester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: t-Butylmalonsaeuremonobenzylester
• 英文别名: 2-((benzyloxy)carbonyl)-3,3-dimethylbutanoic acid；3,3-Dimethyl-2-phenylmethoxycarbonylbutanoic acid
• 化学式: C₁₄H₁₈O₄
• 分子量: 250.295
• InChiKey: MYPJJIPPTUKUAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  t-Butylmalonsaeuremonobenzylester 在 氯化亚砜 、 氢气 作用下， 生成 2-((S)-4-Benzyl-2-oxo-oxazolidine-3-carbonyl)-3,3-dimethyl-butyric acid
  参考文献：
  名称：

  Klotz-Berendes, Bruno; Schaefer, Hans J.; Grehl, Matthias, Angewandte Chemie, 1995, vol. 107, # 2, p. 218 - 220

  摘要：

  DOI：
• 作为产物：
  描述：

  3,3-二甲基-1-丁酸 、 氯甲酸苄酯 在 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.33h， 以73%的产率得到t-Butylmalonsaeuremonobenzylester
  参考文献：
  名称：

  薄荷醇，8-甲基薄荷醇和8-苯基薄荷醇-2-烷基丙二酸酯的非对映选择性阳极杂和均偶联。

  摘要：

  非对映选择性自由基偶联是通过手性助剂实现的。这些自由基是通过五种丙二酸衍生物的阳极脱羧反应生成的。它们是由丙二酸苄酯和四种薄荷醇助剂制备的。在未分开的电池中，在铂电极上与甲醇中的3,3-二甲基丁酸进行共电解，可得到杂耦合产物，产率为22-69％，非对映选择性为5至65％de。没有助酸的电解质以21-50％的产率产生非对映异构体均偶联产物，非对映异构体的比率为1.17：2.00：0.81至7.03：2.00。X射线结构分析和13 C NMR数据证实了新的立体异构中心的立体化学。

  DOI：

  10.3762/bjoc.13.5

文献信息

• NOVEL HYDROXAMIC ACID DERIVATIVES
  申请人：Daiichi Fine Chemical Co., Ltd.

  公开号：EP1179529A1

  公开（公告）日：2002-02-13

  Disclosed are compounds which have not only potent metalloproteinase-inhibiting activity but also amazingly excellent bioavailability and biological activity in vivo, including the property of being well absorbed via oral routes, thereby serving as useful pharmaceuticals, intermediates and processes for the production thereof. The disclosed compounds of the formula (I): wherein R1 is hydrogen, or a hydroxy-protecting group; R2 is hydrogen, or an amino-protecting group; R3, R7, and R8, which may be identical or different, are each independently hydrogen, hydroxy, unsubstituted or optionally substituted (C1-C6) alkyl, or unsubstituted or optionally substituted aryl-(C1-C6) alkyl; R4 is unsubstituted or optionally substituted (C1-C6) alkyl, or unsubstituted or optionally substituted aryl-(C1-C6) alkyl; R5 is hydrogen, unsubstituted or optionally substituted alkyl, unsubstituted or optionally substituted aralkyl, or a carboxy-protecting group; R6 is hydrogen, hydroxy, amino, and a group of the formula: -X-Y wherein X is oxygen, (C1-C6) alkylene or phenylene, Y is a group of the formula: -A-B or -B, wherein A is (C1-C6) alkylene, imino, and (C1-C6) alkyleneimino, and B is hydrogen, amino, amidino, sulfonyl, acylimidoyl, unsubstituted or optionally substituted imidazolyl, unprotected or optionally protected bis(phosphono)methyl or unprotected or optionally protected bis(phosphono)hydroxymethyl; or salts thereof are useful for pharmaceutical and/or veterinary compositions, particularly as metalloproteinase inhibitors which inhibit matrix metalloproteinases or tumor necrosis factor-α-converting enzymes (TNF-α convertases).

  本公开的化合物不仅具有强大的金属蛋白酶抑制活性，而且在体内具有出色的生物利用度和生物活性，包括经口途径吸收良好的特性，因此可用作有用的药物、中间体和生产过程。公开的化合物的结构式（I）如下：其中R1是氢或羟基保护基；R2是氢或氨基保护基；R3、R7和R8可以相同也可以不同，分别独立地是氢、羟基、未取代或可选择取代的（C1-C6）烷基，或未取代或可选择取代的芳基-（C1-C6）烷基；R4是未取代或可选择取代的（C1-C6）烷基，或未取代或可选择取代的芳基-（C1-C6）烷基；R5是氢、未取代或可选择取代的烷基、未取代或可选择取代的芳基烷基，或羧基保护基；R6是氢、羟基、氨基，以及下式的基团：-X-Y，其中X是氧、（C1-C6）烷基或苯基，Y是下式的基团：-A-B或-B，其中A是（C1-C6）烷基、亚胺基和（C1-C6）烷基亚胺基，B是氢、氨基、酰胺基、磺酰基、乙酰亚胺基，未取代或可选择取代的咪唑基，未保护或可选择保护的双（膦酸甲基）或未保护或可选择保护的双（膦酸羟甲基）；或其盐在制药和/或兽医组合物中具有用途，尤其作为抑制基质金属蛋白酶或肿瘤坏死因子-α转化酶（TNF-α转化酶）的金属蛋白酶抑制剂。
• [EN] CARBOSTYRIL DERIVATIVES AS MATRIX METALLOPROTEINASES INHIBITORS<br/>[FR] DERIVES DE CARBOSTYRILE EMPLOYES COMME INHIBITEURS DE METALLOPROTEINASES DE LA MATRICE EXTRACELLULAIRE
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：WO1994021612A1

  公开（公告）日：1994-09-29

  (EN) This invention provides a carbostyril derivative of formula (1), where R1, R2, R3, R4, R5, R6 and n are as defined, or its salt. This carbostyril derivative or its salt possess an excellent matrix metalloproteinases inhibitory action.(FR) Dérivé de carbostyrile de la formule (1), dans laquelle R1, R2, R3, R4, R5, R6 et n sont tels que définis, ou son sel. Ce dérivé de carbostyrile ou son sel possède d'excellentes propriétés de neutralisation des métalloprotéinases de la matrice extracellulaire.

  该发明提供了一种式为（1）的羧基苯基咔唑衍生物，其中R1、R2、R3、R4、R5、R6和n如定义所述，或其盐。该羧基苯基咔唑衍生物或其盐具有出色的基质金属蛋白酶抑制作用。
• Amino acid derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0497192A2

  公开（公告）日：1992-08-05

  The invention provides compounds of the formula wherein A represents the group R1 represents hydrogen, amino, protected amino, acylamino or lower alkyl optionally substituted by aryl, hydroxy, protected hydroxy, amino, protected amino, acylamino, maleimido, succinimido, naphthalimido, 2,3-dihydro-1,3-dioxo-lH-benz[d,e]isoquinol-2-yl, carboxy, protected carboxy, carbamoyl, mono(lower alkyl)-carbamoyl, di(lower alkyl)carbamoyl, di(lower alkyl)amino, carboxy-lower alkanoylamino, pyrrolidino or morpholino; R2 represents hydrogen or lower alkyl optionally substituted by aryl, amino, protected amino, di(lower alkyl)- amino, guanidino, carboxyl, protected carboxyl, carbamoyl, mono(lower alkyl) carbamoyl, di(lower alkyl)-carbamoyl, di(lower alkoxy)phosphinyl, dihydroxyphosphinyl, pyrrolidino, piperidino or morpholino; R3 represents hydrogen or lower alkyl optionally substituted by hydroxy, protected hydroxy, amino or protected amino; R4 represents hydrogen, hydroxy, lower alkoxy or benzyloxy; and R5 represents hydrogen or halogen and their pharmaceutically acceptable salts. These compounds are useful for the control or prevention of degenerative joint diseases or for the treatment of invasive tumours, atherosclerosis or multiple sclerosis. They can be manufactured according to known methods.

  本发明提供了式中化合物 其中 A 代表基团 R1代表氢、氨基、受保护氨基、酰氨基或任选被芳基取代的低级烷基、羟基、受保护羟基、氨基、受保护氨基、酰氨基、马来酰亚胺基、琥珀酰亚胺基、萘酰亚胺基、2、3-二氢-1,3-二氧代-lH-苯并[d,e]异喹啉-2-基、羧基、受保护的羧基、氨基甲酰基、单（低级烷基）氨基甲酰基、二（低级烷基）氨基甲酰基、二（低级烷基）氨基、羧基-低级烷酰氨基、吡咯烷基或吗啉基；R2 代表氢或被芳基、氨基、受保护氨基、二（低级烷基）-氨基、胍基、羧基、受保护羧基、氨基甲酰基、单（低级烷基）氨基甲酰基、二（低级烷基）-氨基甲酰基、二（低级烷氧基）膦酰基、二羟基膦酰基、吡咯烷基、哌啶基或吗啉基任选取代的低级烷基；R3 代表氢或任选被羟基、受保护羟基、氨基或受保护氨基取代的低级烷基；R4 代表氢、羟基、低级烷氧基或苄氧基；R5 代表氢或卤素及其药学上可接受的盐类。这些化合物可用于控制或预防退行性关节疾病，或治疗侵袭性肿瘤、动脉粥样硬化或多发性硬化症。它们可以按照已知的方法制造。
• NOVEL METALLOPROTEINASE INHIBITORS
  申请人：FUJI YAKUHIN KOGYO KABUSHIKI KAISHA

  公开号：EP1038864A1

  公开（公告）日：2000-09-27

  Compounds having not only a high metalloproteinase inhibitory activity but also remarkably improved medicinal applicability in vivo (oral absorbability, etc.) and biological activities and thus being useful a drugs; intermediates in the process for producing the same; and a process for producing these compounds. Specifically, compounds represented by general formula (I) or salts thereof, useful in medicinal and/or veterinary compositions, in particular; metalloproteinase inhibitors inhibiting matrix metalloproteinases and tumor necrosis factor-α (TNF-α) convertase; wherein R1 represents hydrogen or a hydroxy-protective group; R2 represents hydrogen or an amino-protective group; R3, R7 and R8 represent each hydrogen, hydroxy, alkyl, etc.; R4 represents alkyl, arylalkyl, etc.; R5 and R6 are the same or different and each represents hydrogen, alkyl, cycloalkyl, etc.; and R9 represents hydrogen, hydroxy, amino, etc.

  不仅具有较高的金属蛋白酶抑制活性，而且具有明显改善的体内药用性（口服吸收性等）和生物活性，因而可用作药物的化合物；生产这些化合物的中间体；以及生产这些化合物的工艺。具体地说，通式(I)代表的化合物或其盐，可用于药物和/或兽药组合物，特别是；金属蛋白酶抑制剂，可抑制基质金属蛋白酶和肿瘤坏死因子-α（TNF-α）转化酶；其中 R1 代表氢或羟基保护基团；R2 代表氢或氨基保护基团；R3、R7 和 R8 分别代表氢、羟基、烷基等；R4 代表烷基、氨基保护基团、羟基、烷基等。R4 代表烷基、芳烷基等；R5 和 R6 相同或不同，各自代表氢、烷基、环烷基等；R9 代表氢、羟基、氨基等。
• NOVEL REMEDIES FOR ALLERGIC DISEASES
  申请人：FUJI YAKUHIN KOGYO KABUSHIKI KAISHA

  公开号：EP1101492A1

  公开（公告）日：2001-05-23

  Disclosed are anti-inflammatory agents, antiallergic agents, particularly prophylactically and/or therapeutically effective drugs for type I and/or IV allergic conditions, and further pharmaceutical drugs for prophylactically and/or therapeutically treating bronchial asthma, atopic diseases, etc. The inventive drugs comprising a prophylactically and/or therapeutically effective amount of a hydroxamic acid derivative are active in the prophylaxis and/or therapy of allergy, especially type I and/or IV allergy, etc. The drugs are active in prophylactically and/or therapeutically treating inflammation, rhinitis, conjunctivitis, bronchial asthma, atopic diseases (including dermatitis, enteritis, etc.), or allergic gastroenterocolitis (allergic inflammation in digestive tract). The application of such drugs leads to (A) reduction of cells (such as lymphocytes, neutrophils, mast cells, eosinophils, basophils, macrophages and monocytes) at a diseased site, and/or (B) alleviation of inflammatory symptoms caused by migration, infiltration or accumulation of cells (such as lymphocytes, neutrophils, mast cells, eosinophils, basophils, macrophages and monocytes) to (or at) the diseased site, (C) inhibition of pathophysiological functions in cells (such as lymphocytes, neutrophils, mast cells, eosinophils, basophils, macrophages, monocytes, Langerhans cell and dendritic cells), and/or (D) reducing the blood level or inhibiting the production, of antibodies, especially IgE. Accordingly, the drugs are useful in the prophylaxis and/or therapy of diseases, disorders or ill conditions at the site.

  本发明公开了抗炎剂、抗过敏剂，尤其是对 I 型和/或 IV 型过敏症具有预防和/或治疗效果的药物，以及用于预防和/或治疗支气管哮喘、特应性疾病等的进一步药物。包含预防和/或治疗有效量羟肟酸衍生物的本发明药物在预防和/或治疗过敏症，尤其是 I 型和/或 IV 型过敏症等方面具有活性。这些药物在预防和/或治疗炎症、鼻炎、结膜炎、支气管哮喘、特应性疾病（包括皮炎、肠炎等）或过敏性胃肠炎（消化道过敏性炎症）方面具有活性。使用这类药物可(A)减少患病部位的细胞（如淋巴细胞、中性粒细胞、肥大细胞、嗜酸性粒细胞、嗜碱性粒细胞、巨噬细胞和单核细胞），和/或(B)减轻细胞（如淋巴细胞、中性粒细胞、肥大细胞、嗜酸性粒细胞、嗜碱性粒细胞、巨噬细胞和单核细胞）迁移、浸润或积聚引起的炎症症状、(C) 抑制细胞（如淋巴细胞、中性粒细胞、肥大细胞、嗜酸性粒细胞、嗜碱性粒细胞、巨噬细胞、单核细胞、朗格汉斯细胞和树突状细胞）的病理生理功能，和/或 (D) 降低血液中抗体，尤其是 IgE 的水平或抑制其产生。因此，这些药物可用于预防和/或治疗该部位的疾病、失调或病症。