2-Benzyloxycarbonyl-3R-isobutyl-succinic acid 4-tert-butyl ester 1-benzyl ester | 145660-99-7

• 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: 2-Benzyloxycarbonyl-3R-isobutyl-succinic acid 4-tert-butyl ester 1-benzyl ester
• 英文别名: benzyl 2-benzyloxycarbonyl-5-methyl-3R-tert-butoxycarbonylhexanoate；2-benzyloxycarbonyl-3R-tert-butoxycarbonyl-5-methylhexanoic acid benzyl ester；Benzyl (2-benzyloxycarbonyl-3-tert-butoxycarbonyl-5-methyl)hexanoate；1,1,2-Pentanetricarboxylic acid, 4-methyl-, 2-(1,1-dimethylethyl) 1,1-bis(phenylmethyl) ester, (R)-；1-O,1-O-dibenzyl 2-O-tert-butyl 4-methylpentane-1,1,2-tricarboxylate
• CAS: 145660-99-7
• 化学式: C₂₇H₃₄O₆
• 分子量: 454.563
• InChiKey: JIGCQFIWSVEFNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-Benzyloxycarbonyl-3R-isobutyl-succinic acid 4-tert-butyl ester 1-benzyl ester 在 palladium on activated charcoal 哌啶 、 4-氨基吡啶 、 氢气 、 ammonium formate 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (2R,3S)-N4-Benzyloxy-2-isobutyl-3-methyl-N1-((S)-methylcarbamoyl-phenyl-methyl)-succinamide
  参考文献：
  名称：

  Synthesis and biological evaluation of orally active matrix metalloproteinase inhibitors

  摘要：

  The synthesis and biological evaluation of orally active inhibitors of matrix metalloproteinase are reported. Modifications of the P2' position and the a-substituent of hydroxamic acid derivatives were carried out, and revealed that the P2' substituent influenced the MMP inhibitory activities in vitro and in plasma after oral administration. The hydroxamates with phenylglycine at the P2' position were absorbed well orally. Compound 15e, which exhibited the longest duration of inhibitory activity in plasma after oral administration among the phenylglycine derivatives (5a-5d, 15a, 15c, 15e), was evaluated in a rat adjuvant arthritis model. A reduction in hind foot pad swelling and improvements of some inflammatory parameters were demonstrated when the compound was administered orally. These results indicate the potential of MMP inhibitors for rheumatoid arthritis. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00028-x
• 作为产物：
  描述：

  (R)-2-bromo-4-methylpentanoic acid 在 硫酸 、 potassium tert-butylate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 120.0h， 生成 2-Benzyloxycarbonyl-3R-isobutyl-succinic acid 4-tert-butyl ester 1-benzyl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of orally active matrix metalloproteinase inhibitors

  摘要：

  The synthesis and biological evaluation of orally active inhibitors of matrix metalloproteinase are reported. Modifications of the P2' position and the a-substituent of hydroxamic acid derivatives were carried out, and revealed that the P2' substituent influenced the MMP inhibitory activities in vitro and in plasma after oral administration. The hydroxamates with phenylglycine at the P2' position were absorbed well orally. Compound 15e, which exhibited the longest duration of inhibitory activity in plasma after oral administration among the phenylglycine derivatives (5a-5d, 15a, 15c, 15e), was evaluated in a rat adjuvant arthritis model. A reduction in hind foot pad swelling and improvements of some inflammatory parameters were demonstrated when the compound was administered orally. These results indicate the potential of MMP inhibitors for rheumatoid arthritis. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00028-x

文献信息

• Novel method of treatment of inflammatory skin conditions
  申请人：Chandler Rupert Stephen

  公开号：US20070049518A1

  公开（公告）日：2007-03-01

  There is provided, inter alia, a method for the treatment or prevention of an inflammatory skin condition which is characterised by colonisation with Staphylococcus aureus , comprising the topical administration of an aureolysin inhibitor.

  提供了一种治疗或预防由金黄色葡萄球菌定植引起的炎症性皮肤病的方法，包括局部施用一种金黄色葡萄球菌溶素抑制剂。
• Metalloproteinase inhibitors
  申请人：British Biotech Pharmaceuticals Limited

  公开号：US05747514A1

  公开（公告）日：1998-05-05

  The present invention relates to therapeutically active hydroxamic acid and carboxylic acid derivatives, to processes for their preparation, to pharmaceutical compositions containing them, and to the use of such compounds in medicine. In particular, the compounds are inhibitors of metalloproteinases involved in tissue degradation, and in addition are inhibitors of the release of tumor necrosis factor from cells.

  本发明涉及治疗活性的羟羧酸和羧酸衍生物，以及它们的制备方法、含有它们的药物组合物，以及这些化合物在医学上的应用。具体而言，这些化合物是涉及组织降解的金属蛋白酶抑制剂，此外还是细胞中肿瘤坏死因子释放的抑制剂。
• Matrix metalloproteinase inhibitors
  申请人：Pharmacia & Upjohn S.p.A.

  公开号：US06194451B1

  公开（公告）日：2001-02-27

  A compound of formula (I), wherein W is —NHOH or —OH, R1 is either free or protected hydroxymethyl or mercaptomethyl or derivatives thereof, R2 is free or protected hydroxy, R3 and R4 is an organic group, R5 is hydrogen or methyl, or R4 and R5, together with the nitrogen atom to which they are attached, constitute an azaheterocyclyl group, and the solvates, hydrates and pharmaceutically acceptable salts thereof, can inhibit matrix metalloproteinases and the release of tumour necrosis factor (TNF). Processes for producing the compound, intermediates involved in the processes, and pharmaceutical compositions containing the compound are also described.

  化合物的化学式为（I），其中W为—NHOH或—OH，R1为自由或保护的羟甲基或巯基甲基或其衍生物，R2为自由或保护的羟基，R3和R4为有机基团，R5为氢或甲基，或者R4和R5与它们所连接的氮原子一起构成一个氮杂环基团，其溶剂化物、水合物和药学上可接受的盐可以抑制基质金属蛋白酶和肿瘤坏死因子（TNF）的释放。还描述了制备该化合物的过程、涉及该过程的中间体以及含有该化合物的药物组合物。
• Hydroxamino acid based collagenase inhibitors
  申请人：British Bio-technology Limited

  公开号：US05310763A1

  公开（公告）日：1994-05-10

  Compounds of general formula I: ##STR1## wherein: R.sup.1 represents a C.sub.1 -C.sub.6 alkyl, phenyl, thiophenyl, substituted phenyl, phenyl(C.sub.1 -C.sub.6)alkyl, heterocyclyl, (C.sub.1 -C.sub.6)alkylcarbonyl phenacyl or substituted phenacyl group; or, when n=O, R.sup.1 represents SR.sup.x, wherein R.sup.x represents a group: ##STR2## R.sup.2 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, phenyl(C.sub.1 -C.sub.6)alkyl, cycloalkyl(C.sub.1 -C.sub.6)alkyl or cycloalkenyl(C.sub.1 -C.sub.6)alkyl group; R.sup.3 represents an amino acid residue with R or S stereochemistry or a C.sub.1 -C.sub.6 alkyl, benzyl, (C.sub.1 -C.sub.6 alkoxy)benzyl or benzyloxy(C.sub.1 -C.sub.6 alkyl) group; R.sup.4 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl group; R.sup.5 represents a hydrogen atom or a methyl group; n is an integer having the value 0, 1 or 2; and A represents a C.sub.1 -C.sub.6 hydrocarbon chain, optionaly substituted with one or more C.sub.1 -C.sub.6 alkyl, phenyl or substituted phenyl groups; and their salts and N-oxides are collagenase inhibitors are and useful in the management of disease involving tissue degradation and/or the promotion of wound healing. Diseases involving tissue degradation include arthropathy (particularly rheumatoid arthritis), inflammation, dermatological diseases, bone resorption diseases and tumor invasion.

  通式I的化合物：##STR1## 其中：R.sup.1代表C.sub.1-C.sub.6烷基，苯基，噻吩基，取代苯基，苯基（C.sub.1-C.sub.6）烷基，杂环基，（C.sub.1-C.sub.6）烷基羰基苯乙基或取代苯基羰基苯乙基；或者，当n=O时，R.sup.1代表SR.sup.x，其中R.sup.x代表一个基团：##STR2## R.sup.2代表氢原子或C.sub.1-C.sub.6烷基，C.sub.1-C.sub.6烯基，苯基（C.sub.1-C.sub.6）烷基，环烷基（C.sub.1-C.sub.6）烷基或环烯基（C.sub.1-C.sub.6）烷基；R.sup.3代表具有R或S立体化学的氨基酸残基或C.sub.1-C.sub.6烷基，苄基，（C.sub.1-C.sub.6烷氧基）苄基或苄氧（C.sub.1-C.sub.6烷基）基；R.sup.4代表氢原子或C.sub.1-C.sub.6烷基；R.sup.5代表氢原子或甲基；n是一个整数，其值为0、1或2；A代表C.sub.1-C.sub.6碳氢链，可选地取代一个或多个C.sub.1-C.sub.6烷基，苯基或取代苯基基团；其盐和N-氧化物是胶原酶抑制剂，可用于治疗涉及组织降解和/或促进伤口愈合的疾病。涉及组织降解的疾病包括关节病（特别是类风湿性关节炎），炎症，皮肤病，骨吸收疾病和肿瘤侵袭。
• [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。