4-氨基四氢-2H-吡喃-3-羧酸甲酯 | 503168-22-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-氨基四氢-2H-吡喃-3-羧酸甲酯
• 英文名称: (3R,4R)-methyl 4-aminotetrahydro-2H-pyran-3-carboxylate
• 英文别名: methyl (3R,4R)-4-aminooxane-3-carboxylate
• CAS: 503168-22-7
• 化学式: C₇H₁₃NO₃
• 分子量: 159.185
• InChiKey: PLVOQXPMPPTFRW-NTSWFWBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  4-氨基四氢-2H-吡喃-3-羧酸甲酯 在 盐酸羟胺 、 sodium methylate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (3R,4R)-N-hydroxy-4-({4-[(2-methyl-4-quinolinyl)methyl]benzoyl}amino)tetrahydro-2H-pyran-3-carboxamide
  参考文献：
  名称：

  A new 4-(2-methylquinolin-4-ylmethyl)phenyl P1′ group for the β-amino hydroxamic acid derived TACE inhibitors

  摘要：

  A new P1' group for TACE inhibitors was identified by eliminating the oxygen atom in the linker of the original 4-(2methylquinolin-4-ylmethoxy)phenyl P1' group. Incorporation of this 4-(2-methylquinolin-4-ylmethyl)phenyl group onto different beta-aminohydroxamic acid cores provided compound 18, which demonstrated potent porcine TACE (p-TACE) and human whole blood activity, excellent PK properties, and good selectivity against a variety of MMPs. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.041
• 作为产物：
  描述：

  2H-Pyran-3-carboxylic acid, tetrahydro-4-[[(1R)-1-phenylethyl]amino]-,methyl ester 在 palladium dihydroxide 盐酸 、 氢气 作用下， 以 乙醇 为溶剂， 生成 4-氨基四氢-2H-吡喃-3-羧酸甲酯 、 (3S,4S)-4-氨基四氢-2H-吡喃-3-羧酸甲酯
  参考文献：
  名称：

  Discovery of β-benzamido hydroxamic acids as potent, selective, and orally bioavailable TACE inhibitors

  摘要：

  beta-Benzamido hydroxamic acids were discovered as potent TACE inhibitors. A computer model was constructed to help understanding the binding activities and guiding SAR study. SAR optimization led to the discovery of compound 30 which met all in vitro and in vivo criteria for the program and was selected for further evaluation. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.093

文献信息

• [EN] PIPERIDINE DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY<br/>[FR] DÉRIVÉS DE PIPÉRIDINE EN TANT QUE MODULATEURS D'ACTIVITÉ DE RÉCEPTEUR DE CHIMIOKINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2009015166A1

  公开（公告）日：2009-01-29

  The present application describes modulators of MIP-1 of formula (I) : or stereoisomers or pharmaceutically acceptable salts thereof, wherein m, Q, T, W, Z, R1, R3, R4, R5, R5a and R5b, are as set forth above. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis using the modulators are disclosed.

  本申请描述了公式（I）的MIP-1调节剂：或其立体异构体或药用可接受的盐，其中m、Q、T、W、Z、R1、R3、R4、R5、R5a和R5b如上所述。此外，还公开了利用这些调节剂治疗和预防哮喘和过敏性疾病等炎症性疾病，以及类风湿关节炎和动脉粥样硬化等自身免疫病理的方法。
• Potent, exceptionally selective, orally bioavailable inhibitors of TNF-α Converting Enzyme (TACE): Novel 2-substituted-1H-benzo[d]imidazol-1-yl)methyl)benzamide P1′ substituents
  作者：Gregory R. Ott、Naoyuki Asakawa、Zhonghui Lu、Rajan Anand、Rui-Qin Liu、Maryanne B. Covington、Krishna Vaddi、Mingxin Qian、Robert C. Newton、David D. Christ、James M. Trzaskos、James J.-W. Duan

  DOI：10.1016/j.bmcl.2008.01.075

  日期：2008.3

  Novel ((2-substituted-1H-benzo[d]imidazol-1-yl)methyl)benzamides were found to be excellent P1' substituents in conjunction with unique constrained beta-amino hydroxamic acid scaffolds for the discovery of potent selective inhibitors of TNF-alpha Converting Enzyme (TACE). Optimized examples proved potent for TACE, exceptionally selective over a wide panel of MMP and ADAM proteases, potent in the suppression

  发现新型（（2-取代的-1H-苯并[d]咪唑-1-基）甲基）苯甲酰胺是出色的P1'取代基，结合独特的受约束的β-氨基异羟肟酸支架，可发现有效的TNF选择性抑制剂-alpha转换酶（TACE）。优化的实例证明了对TACE的有效作用，对多种MMP和ADAM蛋白酶具有极高的选择性，对抑制人全血中LPS诱导的TNF-α具有有效作用，并且具有口服生物利用度。
• PIPERIDINE DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
  申请人：Santella Joseph B.

  公开号：US20100222366A1

  公开（公告）日：2010-09-02

  The present application describes modulators of MIP-1 of formula (I): or stereoisomers or pharmaceutically acceptable salts thereof, wherein m, Q, T, W, Z, R1, R3, R4, R5, R5a and R5b, are as set forth above. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis using the modulators are disclosed.

  本申请描述了MIP-1的调节剂，其化学式为(I)：或其立体异构体或药学上可接受的盐，其中m、Q、T、W、Z、R1、R3、R4、R5、R5a和R5b如上所述。此外，还公开了使用这些调节剂治疗和预防炎症性疾病，如哮喘和过敏疾病，以及自身免疫病理，如类风湿性关节炎和动脉粥样硬化的方法。
• Potent, selective, orally bioavailable inhibitors of tumor necrosis factor-α converting enzyme (TACE): Discovery of indole, benzofuran, imidazopyridine and pyrazolopyridine P1′ substituents
  作者：Zhonghui Lu、Gregory R. Ott、Rajan Anand、Rui-Qin Liu、Maryanne B. Covington、Krishna Vaddi、Mingxin Qian、Robert C. Newton、David D. Christ、James Trzaskos、James J.-W. Duan

  DOI：10.1016/j.bmcl.2008.01.120

  日期：2008.3

  Potent and selective inhibitors of tumor necrosis factor-a converting enzyme ( TACE) were discovered with several new heterocyclic P1' groups in conjunction with cyclic beta-amino hydroxamic acid scaffolds. Among them, the pyrazolopyridine provided the best overall profile when combined with tetrahydropyran beta-amino hydroxamic acid scaffold. Specifically, inhibitor 49 showed IC50 value of 1 nM against porcine TACE and 170 nM in the suppression of LPS-induced TNF-alpha of human whole blood. Compound 49 also displayed excellent selectivity over a wide panel of MMPs as well as excellent oral bioavailability (F% > 90%) in rat n-in-1 PK studies. (C) 2008 Elsevier Ltd. All rights reserved.
• US8536198B2
  申请人：——

  公开号：US8536198B2

  公开（公告）日：2013-09-17