(2,2,2-trifluoroacetyl) 1-[[4-[(E)-3-(hydroxyamino)-3-oxoprop-1-enyl]phenyl]methylamino]cyclopentane-1-carboxylate

• 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: (2,2,2-trifluoroacetyl) 1-[[4-[(E)-3-(hydroxyamino)-3-oxoprop-1-enyl]phenyl]methylamino]cyclopentane-1-carboxylate
• 化学式: C₁₈H₁₉F₃N₂O₅
• 分子量: 400.3
• InChiKey: YRQFWRNHZHGPEB-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  9

文献信息

• ENZYME INHIBITORS
  申请人：Donald Alastair David Graham

  公开号：US20140155439A1

  公开（公告）日：2014-06-05

  Compounds of formula (I), inhibit HDAC activity: wherein A, B and D independently represent ═CH— or ═N—; W is —CH═CH— Or —CH 2 CH 2 —; R 1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; R 2 and R 3 are selected from the side chains of a natural or non-natural alpha amino acid, provided that neither R 2 nor R 3 is hydrogen, or R 2 and R 3 , taken together with the carbon to which they are attached, form a 3-6 membered saturated cycloalkyl or heterocyclyl ring; Y is a bond, —C(C═O)—, —S(═O) 2 —, —C(C═O)O—, —C(C═O)NR′—, —C(═S)—NR′, —C(═NH)NR′ or —S(═O) 2 NR— wherein R′ is hydrogen or optionally substituted C 1 -C 6 alkyl; L 1 is a divalent radical of formula -(Alk 1 ) m (Q)(Alk 2 ) p — wherein in, n, p, Q, AIk 1 and AIk 2 are as defined in the claims; X 1 represents a bond; —C(═O); or —S(═O) 2 —; —NR 4 C(═O)—, —C(C═O)NR 4 —, —NR 4 C(═O)NR 5 —, —NR 4 S(═O) 2 —, or —S(═O) 2 NR 4 — wherein R 4 and R 5 are independently hydrogen or optionally substituted C 1 -C 6 alkyl; and z is 0 or 1.

  式(I)的化合物抑制HDAC活性，其中A、B和D分别表示═CH—或═N—；W是—CH═CH—或—CH2CH2—；R1是羧酸基（—COOH）或可由一个或多个细胞内羧酯酶水解为羧酸基的酯基；R2和R3选自天然或非天然α-氨基酸的侧链，但R2和R3均不为氢，或R2和R3连同它们所连接的碳形成3-6成员的饱和环烷基或杂环烷基；Y是一键，—C(C═O)—、—S(═O)2—、—C(C═O)O—、—C(C═O)NR′—、—C(═S)—NR′、—C(═NH)NR′或—S(═O)2NR—，其中R′是氢或可选地取代的C1-C6烷基；L1是式-(Alk1)m(Q)(Alk2)p—的二价基团，其中n、m、p、Q、Alk1和Alk2如权利要求中所定义；X1表示一键；—C(═O)；或—S(═O)2—；—NR4C(═O)—、—C(C═O)NR4—、—NR4C(═O)NR5—、—NR4S(═O)2—或—S(═O)2NR4—，其中R4和R5独立地为氢或可选地取代的C1-C6烷基；z为0或1。