R-2-nonyl-succinic acid 4-t-butyl ester | 195823-89-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: R-2-nonyl-succinic acid 4-t-butyl ester
• 英文别名: (2R)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]undecanoic acid
• CAS: 195823-89-3
• 化学式: C₁₇H₃₂O₄
• 分子量: 300.439
• InChiKey: NTZZZXIIHVJIAA-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  21
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 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：

  R-2-nonyl-succinic acid 4-t-butyl ester 在 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-3-((S)-1-Methylcarbamoyl-2-phenyl-ethylcarbamoyl)-dodecanoic acid
  参考文献：
  名称：

  Inhibition of Matrix Metalloproteinases: An examination of the S1′ pocket

  摘要：

  Peptidomimetic carboxylate- and hydroxamate-based inhibitors of matrix metalloproteinases containing extended P1' groups have been prepared. Potent inhibition and good selectivity for MMP-2 has been observed for the compounds produced. (C) 1997, Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(96)00602-6
• 作为产物：
  描述：

  十一烷酰氯 在 lithium hydroxide 、 正丁基锂 、 双氧水 、 lithium diisopropyl amide 、 sodium nitrite 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.42h， 生成 R-2-nonyl-succinic acid 4-t-butyl ester
  参考文献：
  名称：

  Inhibition of Membrane-Type 1 Matrix Metalloproteinase by Hydroxamate Inhibitors:  An Examination of the Subsite Pocket

  摘要：

  The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been reported to mediate the activation of pro-gelatinase A (proMMP-2), which is associated with tumor proliferation and metastasis. MT1-MMP can also digest extracellular matrix (ECM) such as interstitial collagens, gelatin, and proteoglycan and thus may play an important role in pathophysiological digestion of ECM. We studied the inhibitory effect of various hydroxamate MMP inhibitors, including known inhibitors such as BB-94, BB-2516, GM6001, and Ro31-9790, on a deletion mutant of MT1-MMP lacking the transmembrane domain (Delta MT1) to further characterize the enzyme and develop a selective inhibitor for MT1-MMP. The evaluation of the inhibitory activities of various hydroxamates reveals general structural profiles affecting selectivities toward MMPs. In particular, a longer side chain at the P1' position is preferable for the binding to MMP-2, -3, and -9 and MT1-MMP. For the P2' position, an a-branched alkyl group is critical for the binding toward Delta MT1, while the introduction of a bulky group at the a-position of hydroxamic acid seems to diminish the activity against Delta MT1. Summation of the data on the sensitivity of Delta MT1 to various hydroxamate inhibitors indicates that (1) the volume of the S1' subsite of Delta MT1 is similar to that of MMP-2, -3, and -9, which is bigger than that of MMP-1, and (2) the S1 and S2' subsites are narrower than those in other MMPs. On the basis of these results, the hydroxamates with a P1' phenylpropyl and P2' alpha-branched alkyl group were synthesized and evaluated for inhibitory activity. These inhibitors (1h,i) showed strong activity against Delta MT1 over MMP-1, but no selectivity between Delta MT1 and MMP-9. These results are explained using molecular modeling studies conducted on MT1-MMP.

  DOI：

  10.1021/jm970404a
• 作为试剂：
  描述：

  、 L-苯甘氨酸 、 甲胺 、 在 R-2-nonyl-succinic acid 4-t-butyl ester 、 氢氧化锂 、 双氧水 作用下， 以to give 2-(R)-[(tert-butoxycarbonyl)methyl]undecanoyl-L-phenylglycine-N-methylamide (5)的产率得到
  参考文献：
  名称：

  Novel mmp-2/mmp-9 inhibitors

  摘要：

  本发明提供了小说的MMP-2/MMP-9抑制剂及其使用方法。

  公开号：

  US20030225272A1

文献信息

• Rapid Synthesis of Matrix Metalloproteinase Inhibitors via Ugi Four-Component Condensation
  作者：Christopher D. Floyd、Laura A. Harnett、Andrew Miller、Sanjay Patel、Lydia Saroglou、Mark Whittaker

  DOI：10.1055/s-1998-1729

  日期：1998.6

  By employing ammonia, together with a mono succinate ester, an aldehyde and an isonitrile in the Ugi four-component condensation the basic structure of pseudopeptide succinyl matrix metalloproteinase inhibitors is constructed in a single step. Deprotection of the ester provides the carboxylic acid zinc(II) binding group required for biological activity.

  通过在 Ugi 四组份缩合过程中使用氨、琥珀酸单酯、醛和异腈，只需一个步骤就能构建出琥珀酰基基质金属蛋白酶抑制剂的基本结构。酯的去保护作用提供了生物活性所需的羧酸锌（II）结合基团。
• Discovery of potent and selective succinyl hydroxamate inhibitors of matrix metalloprotease-3 (Stromelysin-1)
  作者：M.Jonathan Fray、RogerP Dickinson

  DOI：10.1016/s0960-894x(00)00720-4

  日期：2001.2

  Structure-activity relationships are described for a series of succinyl hydroxamic acids 4a-o as potent and selective inhibitors of matrix metalloprotease-3 (stromelysin-1). Optimisation of P1' and P3' groups gave compound 4j (MMP-3 IC50 = 5.9nM) which was >140-fold less potent against MMP-1 (IC50 = 51,000nM), MMP-2 (IC50=1790nM), MMP-9 (IC50 = 840 nM) and MMP-14 (IC50 = 1900 nM). (C) 2001 Elsevier Science Ltd. All rights reserved.
• EP1283823A4
  申请人：——

  公开号：EP1283823A4

  公开（公告）日：2005-07-27
• NOVEL MMP-2/MMP-9 INHIBITORS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1283823A1

  公开（公告）日：2003-02-19
• [EN] METHODS OF TREATMENT USING DUAL MATRIX-METALLOPROTEINASE-2 AND MATRIX METALLOPROTEINASE-9 INHIBITORS<br/>[FR] PROCEDES DE TRAITEMENT AU MOYEN D'INHIBITEURS DOUBLES DE METALLOPROTEINASE-2 MATRICIELLE ET DE METALLOPROTEINASE-9 MATRICIELLE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2001026671A1

  公开（公告）日：2001-04-19

  The invention relates to a method for treating a patient suffering from pain or stroke, said method comprising the step of administering to the patient a pain-treating effective amount of a dual inhibitor of human MMP-2 (SEQ ID NO:2) and MMP-9 (SEQ ID NO:4) in combination with a carrier.