4-((R)-benzyloxycarbonylamino-methoxycarbonyl-methyl)piperidine-1-carboxylic acid tert-butyl ester | 400888-21-3

• 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: 4-((R)-benzyloxycarbonylamino-methoxycarbonyl-methyl)piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: N-CBZ-(R)-α-(N-BOC-4-piperidinyl)-glycine methyl ester；tert-butyl 4-[(1R)-2-methoxy-2-oxo-1-(phenylmethoxycarbonylamino)ethyl]piperidine-1-carboxylate
• CAS: 400888-21-3
• 化学式: C₂₁H₃₀N₂O₆
• 分子量: 406.479
• InChiKey: QJKSSNRWMGBWPY-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-((R)-benzyloxycarbonylamino-methoxycarbonyl-methyl)piperidine-1-carboxylic acid tert-butyl ester 在 palladium on activated charcoal lithium hydroxide 、 氢气 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 36.0h， 生成 (R)-1-boc-4-(氨基羧基甲基)哌啶
  参考文献：
  名称：

  An enantioselective synthesis of (R)-4-piperidinylglycine

  摘要：

  An efficient process for the synthesis of (R)-N-t-Boc-4-piperidinylglycine 8a, an unnatural amino acid, via enantioselective rhodium-catalyzed hydrogenation of the Cbz-enamide 5a is described. Subsequent deprotection of 8a affords unprotected (R)-4-piperidinylglycine 9 in good yield. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00425-6
• 作为产物：
  描述：

  (±)-Z-α-膦酰甘氨酸三甲酯 在 [Rh((R,R)-Me-BPE)(COD)]-[OTf] 1,1,2,3-四甲基胍 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 20.0 ℃ 、620.53 kPa 条件下， 反应 114.0h， 生成 4-((R)-benzyloxycarbonylamino-methoxycarbonyl-methyl)piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  An enantioselective synthesis of (R)-4-piperidinylglycine

  摘要：

  An efficient process for the synthesis of (R)-N-t-Boc-4-piperidinylglycine 8a, an unnatural amino acid, via enantioselective rhodium-catalyzed hydrogenation of the Cbz-enamide 5a is described. Subsequent deprotection of 8a affords unprotected (R)-4-piperidinylglycine 9 in good yield. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00425-6

文献信息

• Discovery of Potent, Selective, and Orally Active Carboxylic Acid Based Inhibitors of Matrix Metalloproteinase-13
  作者：Lauren G. Monovich、Ruben A. Tommasi、Roger A. Fujimoto、Vincent Blancuzzi、Kirk Clark、Wendy D. Cornell、Robert Doti、John Doughty、James Fang、David Farley、John Fitt、Vishwas Ganu、Ronald Goldberg、Robert Goldstein、Stacey Lavoie、Raviraj Kulathila、William Macchia、David T. Parker、Richard Melton、Elizabeth O’Byrne、Gary Pastor、Theodore Pellas、Elizabeth Quadros、Noela Reel、Dennis M. Roland、Yumi Sakane、Hem Singh、Jerry Skiles、Joseph Somers、Karen Toscano、Andrew Wigg、Siyuan Zhou、Lijuan Zhu、Wen-Chung Shieh、Song Xue、Leslie W. McQuire

  DOI：10.1021/jm801394m

  日期：2009.6.11

  The matrix metalloproteinase enzyme MMP-13 plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). An effective MMP-13 inhibitor would therefore be a novel disease modifying therapy for the treatment of arthritis. Our efforts have resulted in the discovery of a series of carboxylic acid inhibitors of MMP-13 that do not significantly inhibit the related

  基质金属蛋白酶MMP-13在骨关节炎（OA）的软骨和骨骼的II型胶原降解中起关键作用。因此，有效的MMP-13抑制剂将是用于治疗关节炎的新型疾病改良疗法。我们的努力导致发现了一系列MMP-13羧酸抑制剂，它们不会显着抑制相关的MMP-1（胶原酶-1）或肿瘤坏死因子-α（TNF-α）转化酶（TACE）。先前已经提出（但尚未证明）抑制后两种酶可能导致副作用。鉴定出有前途的羧酸铅9并开发了收敛的合成方法。本文介绍了9的优化和化合物24f的鉴定进一步发展。化合物24f是MMP-13的亚纳摩尔抑制剂（IC 50值为0.5 nM，K i为0.19 nM），对MMP-1或TACE无活性（IC 50大于10000 nM）。此外，在MMP-13诱导的软骨降解的大鼠模型中，口服30 mg / kg（75％抑制，p <0.05）和10 mg / kg（40％抑制，p < 0.05）口服后，蛋白24f显着降低蛋白聚糖的释放。0
• Certain azacycloalkyl substituted acetic acid derivatives
  申请人：——

  公开号：US20040235896A1

  公开（公告）日：2004-11-25

  Compounds of the formula (I) wherein R represents OH or NHOH; R 1 represents hydrogen, optionally substituted lower alkyl, aryl-lower alkyl, cycloalkyl-lower alkyl, or acyl derived from a carboxylic acid, from a carbonic acid, from a carbamic acid of from a sulfonic acid; R 2 represents biarylsulfonyl or aryloxyarylsufonyl; R 3 represents hydrogen, optionally substituted lower alkyl, aryl-lower alkyl, cycloalkyl-lower alkyl or acyl derived from a carboxylic acid, from a carbonic acid or form a carbamic acid; R 4 and R 5 represent independently hydrogen, lower alkyl, lower alkoxycarbonyl, aryl-lower alkyl or cycloalkyl-lower alkyl; m is zero, 1, 2 or 3; pharmaceutically acceptable prodrug derivatives thereof; pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; and their use for inhibiting matrix degrading metalloproteinases and preventing or treating matrix metalloproteinase dependent conditions in mammals. 1

  式(I)化合物，其中R代表OH或NHOH；R1代表氢、可选择性取代的低级烷基、芳基-低级烷基、环烷基-低级烷基或源自羧酸、碳酸、氨基甲酸或磺酸的酰基；R2代表双芳基磺酰基或芳氧基芳基磺酰基；R3代表氢、可选择性取代的低级烷基、芳基-低级烷基、环烷基-低级烷基或源自羧酸、碳酸或氨基甲酸的酰基；R4和R5各自独立地代表氢、低级烷基、低级烷氧羰基、芳基-低级烷基或环烷基-低级烷基；m为0、1、2或3；其药学上可接受的药物前体衍生物；其药学上可接受的盐；包含所述化合物的药物组合物；以及它们用于抑制基质降解金属蛋白酶和预防或治疗哺乳动物中依赖基质金属蛋白酶的状况的用途。
• Azacycloalkyl substituted acetic acid derivatives for use as MMP inhibitors
  申请人：Fujimoto Aki Roger

  公开号：US20070060569A1

  公开（公告）日：2007-03-15

  Compound of the formula wherein R represents OH or NHOH; R 1 represents hydrogen, optically substituted lower alkyl, aryl-lower alkyl, cycloalkyl-lower alkyl, or acyl derived from a carboxylic acid, from a carbonic acid, from a carbamic acid or from a sulfonic acid; R 2 represents biarylsulfonyl or aryloxyrylsulfonyl; R 3 represents hydrogen, optionally substituted lower alkyl, aryl-lower alkyl, cycloalkyl-lower alkyl or acyl derived from a carboxylic acid, from a carbonic acid or from a carbamic acid; R 4 and R 5 represent independently hydrogen, lower alkyl, lower alkoxycarbonyl, aryl-lower alkyl or cycloalkyl-lower alkyl; m is zero, 1, 2 or 3; pharmaceutically acceptable prodrug derivatives thereof; pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; and their use for inhibiting matrix degrading metalloproteinases and preventing or treating matrix metalloproteinase dependent conditions in mammals.

  该公式的化合物中，R代表OH或NHOH; R1代表氢、光学取代的较低烷基、芳基-较低烷基、环烷基-较低烷基或由羧酸、碳酸、氨基甲酸或磺酸衍生的酰基; R2代表双芳基磺酰基或芳氧基芳基磺酰基; R3代表氢、可选取代的较低烷基、芳基-较低烷基、环烷基-较低烷基或由羧酸、碳酸或氨基甲酸衍生的酰基; R4和R5分别独立地代表氢、较低烷基、较低烷氧羰基、芳基-较低烷基或环烷基-较低烷基; m为零、1、2或3; 其药物可接受的前药衍生物; 其药物可接受的盐; 包括所述化合物的制药组合物; 以及它们用于抑制基质降解金属蛋白酶并预防或治疗哺乳动物基质金属蛋白酶依赖性疾病的用途。
• AZACYCLOALKYL SUBSTITUTED ACETIC ACID DERIVATIVES FOR USE AS MMP INHIBITORS
  申请人：Novartis AG

  公开号：EP1373262B1

  公开（公告）日：2010-05-12
• [EN] CERTAIN AZACYCLOALKYL SUBSTITUTED ACETIC ACID DERIVATIVES<br/>[FR] DERIVES D'ACIDE ACETIQUE SUBSTITUES AZACYCLOALKYLE
  申请人：NOVARTIS AG

  公开号：WO2002072577A2

  公开（公告）日：2002-09-19

  Compounds of the formula (I) wherein R represents OH or NHOH; R1 represents hydrogen, optionally substituted lower alkyl, aryl-lower alkyl, cycloalkyl-lower alkyl, or acyl derived from a carboxylic acid, from a carbonic acid, from a carbamic acid of from a sulfonic acid; R2 represents biarylsulfonyl or aryloxyarylsufonyl; R3 represents hydrogen, optionally substituted lower alkyl, aryl-lower alkyl, cycloalkyl-lower alkyl or acyl derived from a carboxylic acid, from a carbonic acid or form a carbamic acid; R4 and R5 represent independently hydrogen, lower alkyl, lower alkoxycarbonyl, aryl-lower alkyl or cycloalkyl-lower alkyl; m is zero, 1, 2 or 3; pharmaceutically acceptable prodrug derivatives thereof; pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; and their use for inhibiting matrix degrading metalloproteinases and preventing or treating matrix metalloproteinase dependent conditions in mammals.