tert-butyl (2R)-1,2-dibenzyl 4-methylpentane-1,1,2-tricarboxylate | 184948-24-1

• 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: tert-butyl (2R)-1,2-dibenzyl 4-methylpentane-1,1,2-tricarboxylate
• 英文别名: dibenzyl 3(RS)-tert-butyloxycarbonyl-2(R)-iso-butylsuccinate；2-Benzyloxycarbonyl-3R-isobutyl succinic acid-4-benzyl ester-1-tert-butyl ester；dibenzyl 3(RS)-tert-butyloxycarbonyl-2(R)-isobutylsuccinate；Dibenzyl 3(RS)-tert-butoxycarbonyl-2(R)-isobutylsuccinate；1-O,2-O-dibenzyl 1-O-tert-butyl (2R)-4-methylpentane-1,1,2-tricarboxylate
• CAS: 184948-24-1
• 化学式: C₂₇H₃₄O₆
• 分子量: 454.563
• InChiKey: DDBVMIMQIZGFBZ-WTQRLHSKSA-N

物化性质

• 沸点：
  533.7±40.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

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：

  tert-butyl (2R)-1,2-dibenzyl 4-methylpentane-1,1,2-tricarboxylate 在 palladium on activated charcoal 哌啶 、 氢气 作用下， 以 乙醇 、 水 为溶剂， 反应 15.0h， 生成 (2R)-2-[1-(tert-butoxycarbonyl)vinyl]-4-methylpentanoic acid
  参考文献：
  名称：

  Synthesis of an Inhibitor-Tethered Resin for Detection of Active Matrix Metalloproteinases Involved in Disease

  摘要：

  Matrix metalloproteinases ( MMPs), of which 26 members are known in humans, are implicated in a number of diseases. Their activity is strictly controlled, but when the biological control over the activity is lost, disease processes set in. In an attempt to delineate what MMP activity has gone awry in what diseases, including metastatic cancers that are of special interest to our laboratories, we conceived and synthesized two chromatographic resins incorporated with a multifunctional broad- spectrum inhibitor for MMPs. The broad-spectrum inhibitor contains three sterogentic centers and was synthesized in 13 steps. Two structural variants of the inhibitors were linked to the polymer support via disulfide moieties. These resins are intended for use in cellular systems to selectively fish out from a complex mixture of all cellular proteins the active MMP forms important for the specific disease for identification.

  DOI：

  10.1021/jo060058h
• 作为产物：
  描述：

  D-亮氨酸 在 tert-butoxide 、 氢溴酸 、 对甲苯磺酸 、 sodium nitrite 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 20.0h， 生成 tert-butyl (2R)-1,2-dibenzyl 4-methylpentane-1,1,2-tricarboxylate
  参考文献：
  名称：

  Highly water-soluble matrix metalloproteinases inhibitors and their effects in a rat adjuvant-induced arthritis model

  摘要：

  A new series of succinate-based dual inhibitors against matrix metalloproteinases (MMPs) and tumor necrosis factor or. converting enzyme (TACE) possessing highly-water solubility was designed, synthesized, and evaluated for enzyme inhibition. Incorporating of acidic or basic functional groups at the P-2' position afforded sufficient water solubility without significant loss of inhibitory potencies. Compound 18e, which had a guanidino group at the P-2' position as the basic functional group, exhibited broad inhibition against target enzymes for a relatively long period in rat plasma (beta1(1/2): 2.0 h) after sc administration when compared with compounds possessing acidic functional groups (18a and 18b). Consequently, the representative compound 18e together with compound 18b. Marimastat and Trocade were evaluated in the rat adjuvant-induced arthritis model, a model of chronic cartilage destruction. It is concluded that the newly synthesized highly water-soluble compound 18e showed significant activity in suppressing hindpaw swelling and the bone destruction with a minimal administration period (days 3-7). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00109-8

文献信息

• Sulfonic acid derivatives of hydroxamic acids and their use as medicinal products
  申请人：——

  公开号：US20030176486A1

  公开（公告）日：2003-09-18

  The present invention relates to a novel sulfonic acid derivative of hydroxamic acid or a pharmacologically acceptable salt thereof. More particularly, the present invention relates to a sulfonic acid derivative of hydroxamic acid or a pharmacologically acceptable salt thereof, which is useful as an inhibitor of lipopolysaccharides (LPS). In addition, the present invention relates to a novel intermediate compound useful for the synthesis of this sulfonic acid derivative of hydroxamic acid.

  本发明涉及羟羰酸的新型磺酸衍生物或其药理学上可接受的盐。更具体地，本发明涉及一种羟羰酸的磺酸衍生物或其药理学上可接受的盐，其用作脂多糖（LPS）的抑制剂。此外，本发明涉及一种新型中间化合物，用于合成这种羟羰酸的磺酸衍生物。
• 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。
• Method of treating joint disorders using hydroxamic derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US05447929A1

  公开（公告）日：1995-09-05

  Hydroxamic acid derivatives of the fdrrnula ##STR1## and pharmaceutically acceptable salts thereof, which are collagenase inhibitors useful for the control or prevention of degenerative joint diseases, such as, rheumatoid arthritis and ostecarthritis or for the treatment of invasive tumours, atherosclerosis or multiple sclerosis, are described. Said compounds can be prepared either by hyclroxamidating a corresponding carboxylic acid or deprotecting a corresponding benzyloxycarbamoyl compound.

  本文介绍了化学式为##STR1##的羟肟酸衍生物及其药学上可接受的盐，这些衍生物是胶原酶抑制剂，可用于控制或预防退行性关节疾病，如类风湿性关节炎和骨关节炎，或用于治疗侵袭性肿瘤、动脉粥样硬化或多发性硬化症。这些化合物可以通过羟肟化相应的羧酸或去保护相应的苄氧羰基化合物制备。
• Amino acid derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US05304549A1

  公开（公告）日：1994-04-19

  Compounds of the formula ##STR1## wherein A is the group ##STR2## R.sup.1 is 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-1H-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; R.sup.2 is 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; R.sup.3 is hydrogen or lower alkyl optionally substituted by hydroxy, protected hydroxy, amino or protected amino; R.sup.4 is hydrogen, hydroxy, lower alkoxy or benzyloxy; and R.sup.5 is hydrogen or halogen and their pharmaceutically acceptable salts, which are useful for the control or prevention of degenerative joint diseases or for the treatment of invasive tumors, atherosclerosis or multiple sclerosis are described.

  化合物的公式为##STR1##其中A是##STR2##R.sup.1是氢，氨基，保护氨基，酰胺基或较低的烷基，可选地被芳基，羟基，保护羟基，氨基，保护氨基，酰胺基，马来酰亚胺，琥珀酰亚胺，萘啉酰亚胺，2,3-二氢-1,3-二氧-1H-苯[d，e]异喹啉-2-基，羧基，保护羧基，氨基甲酰基，单（较低烷基）氨基甲酰基，双（较低烷基）氨基甲酰基，双（较低烷氧基）膦酰基，二羟基膦酰基，吡咯烷基或吗啉基; R.sup.2是氢或较低烷基，可选地被芳基，氨基，保护氨基，双（较低烷基）-氨基，鸟氨酸基，保护鸟氨酸基，氨基甲酰基，单（较低烷基）氨基甲酰基，双（较低烷基）氨基甲酰基，二（较低烷氧基）膦酰基，二羟基膦酰基，吡咯烷基，哌啶基或吗啉基; R.sup.3是氢或较低烷基，可选地被羟基，保护羟基，氨基或保护氨基取代; R.sup.4是氢，羟基，较低烷氧基或苄氧基; R.sup.5是氢或卤素及其药学上可接受的盐，对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有用。
• Hydroxamic derivatives and pharmaceutical compositions
  申请人：Hoffmann-La Roche Inc.

  公开号：US05318964A1

  公开（公告）日：1994-06-07

  Hydroxamic acid derivatives of the formula ##STR1## and pharmaceutically acceptable salts thereof, which are collagenase inhibitors useful for the control or prevention of degenerative joint diseases, such as, rheumatoid arthritis and osteoarthritis or for the treatment of invasive tumors, atherosclerosis or multiple sclerosis, are described. Said compounds can be prepared either by hydroxamidating a corresponding carboxylic acid or deprotecting a corresponding benzyloxycarbamoyl compound.

  本文介绍了式子## STR1##和其药学上可接受的盐的羟肟酸衍生物，它们是胶原酶抑制剂，可用于控制或预防退行性关节疾病，如类风湿性关节炎和骨关节炎，或用于治疗侵袭性肿瘤、动脉硬化或多发性硬化症。这些化合物可以通过将相应的羧酸羟肟化或去保护相应的苄氧羰基化合物来制备。