(E)-N-hydroxy-3-{1'-acetyl-4-oxospiro[chromane-2,4'-piperidine]-7-yl}acrylamide | 1192125-89-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-N-hydroxy-3-{1'-acetyl-4-oxospiro[chromane-2,4'-piperidine]-7-yl}acrylamide
• 英文别名: (E)-3-{1'-acetyl-4-oxo-spiro[chromane-2,4'-piperidine]-7-yl}-N-hydroxy-acrylamide；(E)-3-(1'-acetyl-4-oxospiro[3H-chromene-2,4'-piperidine]-7-yl)-N-hydroxyprop-2-enamide
• CAS: 1192125-89-5
• 化学式: C₁₈H₂₀N₂O₅
• 分子量: 344.367
• InChiKey: DVBORYWVVLAIIQ-HWKANZROSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (E)-3-(4-oxo-spiro[chromane-2,4'-piperidine]-7-yl)-acrylic acid methyl ester hydrochloride 在 盐酸 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 (E)-N-hydroxy-3-{1'-acetyl-4-oxospiro[chromane-2,4'-piperidine]-7-yl}acrylamide
  参考文献：
  名称：

  基于螺哌啶异羟肟酸的衍生物的发现，合成和药理学评价，其为结构上新颖的组蛋白脱乙酰基酶（HDAC）抑制剂

  摘要：

  通过将特权结构与异羟肟酸部分作为锌结合基团结合，已鉴定出新的作为[HDAC]抑制剂的螺[chromane-2,4'-哌啶]和螺[苯并呋喃-2,4'-哌啶]异羟肟酸衍生物。评价了这些化合物抑制核提取物HDAC的能力以及它们在不同肿瘤细胞系上的体外抗增殖活性。这项工作导致了螺环30d的发现，该螺环在HCT-116鼠异种移植模型中显示出良好的口服生物利用度和肿瘤生长抑制作用。

  DOI：

  10.1021/jm200146u

文献信息

• Spirocyclic derivatives as histone deacetylase inhibitors
  申请人：DAC S.r.l.

  公开号：EP2110377A1

  公开（公告）日：2009-10-21

  This invention is related to new histone deacetylase inhibitors according to the general formula (I) wherein: the dotted line is an optional additional bond; n is zero or an integer from 1 to 4; R1 is hydrogen; C1-C6 alkyl, optionally substituted by aryl or by heteroaryl; (CO)R3; (SO2)R4; aryl; or heteroaryl; R2 is C1-C6 alkyl, optionally substituted by aryl or by heteroaryl; aryl; heteroaryl; or (CO)R5; X is CH2, oxygen or NR6; Y is a bond, CHR7 or NR8; Z is oxygen, CR9R10 or C=R11; and R3, R4, R5, R6, R3 R8, R9, R10 and R11 are as further defined in the specification; and pharmaceutical acceptable salts thereof.

  这项发明涉及新的组蛋白去乙酰化酶抑制剂，其一般公式为（I），其中：虚线是可选的附加键；n为零或1至4之间的整数；R1为氢；C1-C6烷基，可选地被芳基或杂环烷基取代；（CO）R3；（SO2）R4；芳基；或杂环烷基；R2为C1-C6烷基，可选地被芳基或杂环烷基取代；芳基；杂环烷基；或（CO）R5；X为CH2，氧或NR6；Y为键，CHR7或NR8；Z为氧，CR9R10或C=R11；而R3、R4、R5、R6、R3、R8、R9、R10和R11如规范中进一步定义；以及其药用可接受的盐。
• SPIROCYCLIC DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS
  申请人：Varasi Mario

  公开号：US20140080823A1

  公开（公告）日：2014-03-20

  This invention is related to new histone deacetylase inhibitors according to the general formula (I) wherein: the dotted line is an optional additional bond; n is zero or an integer from 1 to 4; R 1 is hydrogen; C 1 -C 6 alkyl, optionally substituted by cycloalkyl, aryl or by heteroaryl; (CO)R 3 ; (SO 2 )R 4 ; cycloalkyl; aryl; or heteroaryl; R 2 is C 1 -C 6 alkyl, optionally substituted by aryl or by heteroaryl; aryl; heteroaryl; or (CO)R 5 ; X is CH 2 , oxygen or NR 6 ; Y is a bond, CHR 7 or NR 8 ; Z is oxygen, CR 9 R 10 or C═R 11 ; and R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are as further defined in the specification; and pharmaceutical acceptable salts thereof.

  本发明涉及新的组蛋白去乙酰化酶抑制剂，其通式为(I)，其中：虚线是可选的额外键；n为零或1至4的整数；R1为氢；C1-C6烷基，可选地被环烷基、芳基或杂芳基取代；(CO)R3；(SO2)R4；环烷基；芳基；或杂芳基；R2为C1-C6烷基，可选地被芳基或杂芳基取代；芳基；杂芳基；或(CO)R5；X为CH2、氧或NR6；Y为键、CHR7或NR8；Z为氧、CR9R10或C═R11；而R3、R4、R5、R6、R7、R8、R9、R10和R11如规范中所进一步定义的；以及其药学上可接受的盐。
• US8592444B2
  申请人：——

  公开号：US8592444B2

  公开（公告）日：2013-11-26
• US9115148B2
  申请人：——

  公开号：US9115148B2

  公开（公告）日：2015-08-25
• [EN] SPIROCYCLIC DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS<br/>[FR] DÉRIVÉS SPIROCYCLIQUES SERVANT D'INHIBITEURS DE L'HISTONE DÉSACÉTYLASE
  申请人：DAC SRL

  公开号：WO2009127609A1

  公开（公告）日：2009-10-22

  This invention is related to new histone deacetylase inhibitors according to the general formula (I) wherein: the dotted line is an optional additional bond; n is zero or an integer from 1 to 4; R1 is hydrogen; C1-C6 alkyl, optionally substituted by cycloalkyl, aryl or by heteroaryl; (CO)R3; (SO2)R4; cycloalkyl; aryl; or heteroaryl; R2 is C1-C6 alkyl, optionally substituted by aryl or by heteroaryl; aryl; heteroaryl; or (CO)R5; X is CH2, oxygen or NR6; Y is a bond, CHR7 or NR8; Z is oxygen, CR9R10 or C=R11; and R3, R4, R5, R6, R7, R8, R9, R10 and R11 are as further defined in the specification; and pharmaceutical acceptable salts thereof.