2(R)-tert-butoxycarbonylaminohexanal | 169448-55-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2(R)-tert-butoxycarbonylaminohexanal
• 英文别名: (R)-tert-butyl 1-oxohexan-2-ylcarbamate；tert-butyl N-[(2R)-1-oxohexan-2-yl]carbamate
• CAS: 169448-55-9
• 化学式: C₁₁H₂₁NO₃
• 分子量: 215.293
• InChiKey: OBMGXPJNZKYOQY-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2(R)-tert-butoxycarbonylaminohexanal 在 盐酸 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 1.5h， 生成 [(E,4R)-1-oxo-1-phenylmethoxyoct-2-en-4-yl]azanium;chloride
  参考文献：
  名称：

  Inhibition of Group IVA Cytosolic Phospholipase A₂ by Novel 2-Oxoamides in Vitro, in Cells, and in Vivo

  摘要：

  The Group IVA cytosolic phospholipase A(2) (GIVA PLA(2)) is a particularly attractive target for drug development because it is the rate-limiting provider of proinflammatory mediators. We previously reported the discovery of novel 2-oxoamides that inhibit GIVA PLA(2) [Kokotos, G.; et al. J. Med. Chem. 2002, 45, 2891-2893]. In the present work, we have further explored this class of inhibitors and found that the 2-oxoamide functionality is more potent when it contains a long 2-oxoacyl residue and a free carboxy group. Long-chain 2-oxoamides based on gamma-aminobutyric acid and gamma-norleucine are potent inhibitors of GIVA PLA(2). Such inhibitors act through a fast and reversible mode of inhibition in vitro, are able to block the production of arachidonic acid and prostaglandin E-2 in cells, and demonstrate potent in vivo antiinflammatory and analgesic activity.

  DOI：

  10.1021/jm030485c
• 作为产物：
  描述：

  叔丁氧羰酰基D-正亮氨酸 在 pyridine-SO3 complex 、 二甲基亚砜 、 三乙胺 、 红铝 作用下， 以 甲苯 为溶剂， 生成 2(R)-tert-butoxycarbonylaminohexanal
  参考文献：
  名称：

  3-氨基-2-羟酰胺和相关化合物作为蛋氨酸氨基肽酶-2的抑制剂。

  摘要：

  取代的3-氨基-2-羟基酰胺和相关的羟基酰胺和酰基肼被鉴定为人甲硫氨酸氨基肽酶2（MetAP2）的抑制剂。通过平行合成和基于迭代结构的设计检查取代基，可以鉴定出对MetAP1具有良好选择性的强效抑制剂。二酰基肼3t（A-357300）被鉴定为对人微血管内皮细胞（HMVEC）的蛋氨酸加工和细胞增殖具有抑制作用的类似物。

  DOI：

  10.1016/j.bmcl.2003.12.031

文献信息

• Inhibitors of farnesyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US05736539A1

  公开（公告）日：1998-04-07

  The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras. The compounds of formula A are representative of the compounds of the present invention: ##STR1##

  本发明涉及抑制法尼基-蛋白转移酶（FTase）和致癌基因蛋白Ras的法尼酰化的化合物。该发明进一步涉及含有本发明化合物的化疗组合物以及抑制法尼基-蛋白转移酶和致癌基因蛋白Ras的方法。式A的化合物代表了本发明的化合物：##STR1##
• 3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2
  作者：George S. Sheppard、Jieyi Wang、Megumi Kawai、Nwe Y. BaMaung、Richard A. Craig、Scott A. Erickson、Linda Lynch、Jyoti Patel、Fan Yang、Xenia B. Searle、Pingping Lou、Chang Park、Ki H. Kim、Jack Henkin、Richard Lesniewski

  DOI：10.1016/j.bmcl.2003.12.031

  日期：2004.2

  and related hydroxyamides and acylhydrazines were identified as inhibitors of human methionine aminopeptidase-2 (MetAP2). Examination of substituents through parallel synthesis and iterative structure-based design allowed the identification of potent inhibitors with good selectivity against MetAP1. Diacylhydrazine 3t (A-357300) was identified as an analogue displaying inhibition of methionine processing

  取代的3-氨基-2-羟基酰胺和相关的羟基酰胺和酰基肼被鉴定为人甲硫氨酸氨基肽酶2（MetAP2）的抑制剂。通过平行合成和基于迭代结构的设计检查取代基，可以鉴定出对MetAP1具有良好选择性的强效抑制剂。二酰基肼3t（A-357300）被鉴定为对人微血管内皮细胞（HMVEC）的蛋氨酸加工和细胞增殖具有抑制作用的类似物。
• PHARMACEUTICAL COMPOSITION FOR TREATMENT OF DISEASES ASSOCIATED WITH DECREASE IN BONE MASS COMPRISING EP4 AGONIST AS ACTIVE INGREDIENT
  申请人：Maruyama Toru

  公开号：US20120202773A1

  公开（公告）日：2012-08-09

  A pharmaceutical composition for topical administration for prevention and/or treatment of diseases associated with decrease in bone mass comprising an EP 4 agonist as an active ingredient. An EP 4 agonist, in which includes a compound possessing prostaglandin skeleton as a representative, possesses promoting action on bone formation, so it is useful for prevention and/or treatment of diseases associated with decrease in bone mass (bone diseases such as primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss and bone necrosis, postoperative osteogenesis, alternative therapy for bone grafting).

  一种用于局部给药预防和/或治疗与骨量减少相关疾病的制药组合物，其包括EP4激动剂作为活性成分。EP4激动剂，其中包括具有前列腺素骨架的化合物作为代表，具有促进骨形成的作用，因此对于预防和/或治疗与骨量减少相关的疾病（如原发性骨质疏松症、继发性骨质疏松症、癌症骨转移、高钙血症、帕吉特病、骨丢失和骨坏死、术后成骨、骨移植的替代疗法）非常有用。
• Structure–activity relationships of natural and non-natural amino acid-based amide and 2-oxoamide inhibitors of human phospholipase A2 enzymes
  作者：Georgia Antonopoulou、Efrosini Barbayianni、Victoria Magrioti、Naomi Cotton、Daren Stephens、Violetta Constantinou-Kokotou、Edward A. Dennis、George Kokotos

  DOI：10.1016/j.bmc.2008.10.046

  日期：2008.12.15

  A variety of 2-oxoamides and related amides based on natural and non-natural amino acids were synthesized. Their activity on two human intracellular phospholipases (GIVA cPLA(2) and GVIA iPLA(2)) and one human secretory phospholipase (GV sPLA(2)) was evaluated. We show that an amide based on (R)-gamma-norleucine is a highly selective inhibitor of GV sPLA2. (C) 2008 Elsevier Ltd. All rights reserved.
• Novel 2-Oxoamide Inhibitors of Human Group IVA Phospholipase A₂
  作者：George Kokotos、Stavroula Kotsovolou、David A. Six、Violetta Constantinou-Kokotou、Christopher C. Beltzner、Edward A. Dennis

  DOI：10.1021/jm025538p

  日期：2002.7.1

  A novel class of potent human cytosolic phospholipase A(2) (GIVA PLA(2)) inhibitors was developed. These inhibitors were designed to contain the 2-oxoamide functionality and a free carboxyl group. Among the compounds tested, a long-chain 2-oxoamide containing L-gamma-norleucine was the most potent inhibitor, causing a 50% decrease in GIVA PLA2 activity at 0.009 mole fraction.