cyclopentyl (2S)-amino(phenyl)acetate | 205180-16-1

• 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: cyclopentyl (2S)-amino(phenyl)acetate
• 英文别名: (S)-phenylglycine cyclopentyl ester；L-phenylglycine cyclopentylester；(S)-Amino-phenyl-acetic acid cyclopentyl ester；cyclopentyl (2S)-2-amino-2-phenylacetate
• CAS: 205180-16-1
• 化学式: C₁₃H₁₇NO₂
• 分子量: 219.283
• InChiKey: WXGVMWCVLJRTIC-LBPRGKRZSA-N

物化性质

• 沸点：
  324.0±22.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  cyclopentyl (2S)-amino(phenyl)acetate 、 3-硝基溴苄 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 (S)-[(3-nitro-benzyl)-amino]-phenyl-acetic acid cyclopentyl ester
  参考文献：
  名称：

  WO2006/117567

  摘要：

  公开号：
• 作为产物：
  描述：

  L-苯甘氨酸 、 cyclopentyl leucinate 生成 cyclopentyl (2S)-amino(phenyl)acetate
  参考文献：
  名称：

  ENZYME AND RECEPTOR MODULATION

  摘要：

  将α-氨基酸酯共价连接到靶向细胞内酶或受体活性调节剂上，其中共轭物的酯基可被一个或多个细胞内羧酸酯酶水解为相应的酸，导致羧酸水解产物在细胞内积累，并相对于未共轭的调节剂实现改善或更长时间的酶或受体调节。

  公开号：

  US20150126534A1

文献信息

• Synthesis, Biological Evaluation, and Molecular Docking of Combretastatin and Colchicine Derivatives and their hCE1‐Activated Prodrugs as Antiviral Agents
  作者：Michael Richter、Veaceslav Boldescu、Dominik Graf、Felix Streicher、Anatoli Dimoglo、Ralf Bartenschlager、Christian D. Klein

  DOI：10.1002/cmdc.201800641

  日期：2019.2.19

  these compounds. Herein we report prodrugs based on combretastatin and colchicine derivatives that contain an ester cleavage site for human carboxylesterase, a highly abundant enzyme in monocytes and hepatocytes targeted by DENV. Relative to their parent compounds, the cytotoxicity of these prodrugs was reduced by several orders of magnitude. All synthesized prodrugs containing a leucine ester were hydrolyzed

  最近的研究表明，微管蛋白可能是登革热（DENV）和寨卡病毒（ZIKV）等载体传播的黄病毒的宿主因子，并且已证明微管蛋白聚合抑制剂（例如秋水仙碱）会减少病毒复制。但是，毒性限制了这些化合物的应用。在本文中，我们报道了基于康普他汀和秋水仙碱衍生物的前药，其包含人羧酸酯酶的酯裂解位点，人羧酸酯酶是DENV靶向的单核细胞和肝细胞中高度丰富的酶。相对于其母体化合物，这些前药的细胞毒性降低了几个数量级。所有含有亮氨酸酯的合成前药在体外都被酯酶水解。与以前的报道相反，苯甘氨酸酯未被人的羧酸酯酶切割。在低微摩尔和亚微摩尔浓度下，观察到了康布雷他汀，秋水仙碱和某些前药对细胞培养物中DENV和ZIKV的抗病毒活性。另外，进行对接研究以了解所研究化合物与微管蛋白的结合模式。
• [EN] INHIBITORS OF HSP90<br/>[FR] INHIBITEURS D'HSP90
  申请人：CHROMA THERAPEUTICS LTD

  公开号：WO2010043865A1

  公开（公告）日：2010-04-22

  The invention provides a compound which is (a) a pyrrolopyrimidine derivative of formula (I) or a tautomer thereof, or (b) a pharmaceutically acceptable salt, N-oxide, hydrate or solvate thereof: Formula (I) wherein R1, R2, R3, R4 and W are as defined herein. The compounds are useful in the treatment of diseases mediated b HSP90 and also in the treatment of inflammation.

  该发明提供了一种化合物，该化合物是(a) 公式(I)的吡咯吡嘧啶衍生物或其互变异构体，或者(b) 该化合物的药用可接受的盐、N-氧化物、水合物或溶剂化合物：公式(I)其中R1、R2、R3、R4和W如本文所定义。这些化合物在治疗由HSP90介导的疾病以及治疗炎症方面是有用的。
• [EN] P38 MAP KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA MAP KINASE P38
  申请人：CHROMA THERAPEUTICS LTD

  公开号：WO2009060160A1

  公开（公告）日：2009-05-14

  Compounds of formula (I) are inhibitors of p38 MAP kinase, and are therefore of utility in the treatment of, inter alia, inflammatory conditions including rheumatoid arthritis and COPD: formula (I) wherein: G is -N= or -CH=; D is an optionally substituted divalent mono- or bi-cyclic aryl or heteroaryl radical having 5 - 13 ring members; R6 is hydrogen or optionally substituted C1-C3 alkyl; P represents hydrogen and U represents a radical of formula (IA); or U represents hydrogen and P represents a radical of formula -A-(CH2)z-X1-L1 -Y-NH-CHR1R2 wherein A represents an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5 - 13 ring members; z, Y, L1, and X1 are as defined in the specification; R1 is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular esterase enzymes to a carboxylic acid group; and R2 is the side chain of a natural or non-natural alpha amino acid.

  公式（I）的化合物是p38 MAP激酶的抑制剂，因此在治疗炎症性疾病包括类风湿性关节炎和COPD方面具有效用：公式（I）其中：G是-N =或-CH =; D是具有5-13个环成员的可选取代的二价单环或双环芳基或杂芳基基团; R6是氢或可选取代的C1-C3烷基; P代表氢，U代表公式（IA）的基团;或U代表氢，P代表公式-A-（CH2）z-X1-L1-Y-NH-CHR1R2的基团，其中A代表具有5-13个环成员的可选取代的二价单环或双环碳环或杂环基团; z，Y，L1和X1如规范中定义; R1是羧酸基（-COOH）或可由一个或多个细胞内酯酶酶水解为羧酸基的酯基;而R2是天然或非天然α氨基酸的侧链。
• ENZYME INHIBITORS
  申请人：Davidson Alan Hornsby

  公开号：US20140163042A1

  公开（公告）日：2014-06-12

  Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R 1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R 2 is the side chain of a natural or non-natural alpha amino acid; Y is a bond, —C(═O), —S(═O) 2 —, —C(═O)O—, —C(O)NR 3 —, —C(═S)—NR 3 , —C(═NH)NR 3 or —S(═O) 2 NR 3 — wherein R 3 is hydrogen or optionally substituted C 1 -C 6 alkyl; L 1 is a divalent radical of formula -(Alk 1 ) m (Q) n (Alk 2 ) p - wherein m, n and p are independently 0 or 1, Q is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, or (ii), in the case where both m and p are 0, a divalent radical of formula —X 2 -Q 1 - or -Q 1 -X 2 — wherein X 2 is —O—, S— or NR A — wherein R A is hydrogen or optionally substituted C 1 -C 3 alkyl, and Q 1 is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, Alk 1 and Alk 2 independently represent optionally substituted divalent C 3 -C 7 cycloalkyl radicals, or optionally substituted straight or branched, C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene radicals which may optionally contain or terminate in an ether (—O—), thioether (—S—) or amino (—NR A —) link wherein R A is hydrogen or optionally substituted C 1 -C 3 alkyl; X 1 represents a bond; —C(═O); or —S(═O) 2 —; —NR 4 C(═O)—, —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; z is 0 or 1; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R 1 R 2 NH—Y-L 1 -X 1 -[CH 2 ] Z — and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent linker radical linking a ring atom in A with the hydroxamic acid group CONIIOII, the length of the linker radical, from the terminal atom linked to the ring atom of A to the terminal atom linked to the hydroxamic acid group, is equivalent to that of an unbranched saturated hydrocarbon chain of from 3-10 carbon atoms.

  式(I)的化合物是组蛋白去乙酰化酶活性抑制剂，可用于治疗癌症等疾病，其中R1是羧酸基（-COOH）或可由一个或多个细胞内羧酸酯酶水解为羧酸基的酯基；R2是天然或非天然α氨基酸的侧链；Y是键，-C（=O），-S（=O）2-，-C（=O）O-，-C（=O）NR3-，-C（=S）-NR3，-C（=NH）NR3或-S（=O）2NR3-，其中R3是氢或可选取代的C1-C6烷基；L1是式-(Alk1)m(Q)n(Alk2)p-的二价基团，其中m、n和p独立地为0或1，Q是（i）一个可选取代的二价单环或双环碳环或杂环基团，具有5-13个环成员，或（ii）在m和p均为0的情况下，是式-Q1-X2-或-X2-Q1-的二价基团，其中X2是-O-，-S-或-NRA-，其中RA是氢或可选取代的C1-C3烷基，Q1是可选取代的二价单环或双环碳环或杂环基团，具有5-13个环成员，Alk1和Alk2独立地表示可选取代的二价C3-C7环烷基基团，或可选取代的直链或支链，C1-C6烷基，C2-C6烯基或C2-C6炔基基团，其可以可选地含有或终止于醚（-O-），硫醚（-S-）或氨基（-NRA-）链，其中RA是氢或可选取代的C1-C3烷基；X1表示键，-C（=O）或-S（=O）2-；-NR4C（=O）-，-C（=O）NR4-，-NR4C（=O）NR5-，-NR4S（=O）2-或-S（=O）2NR4-，其中R4和R5独立地为氢或可选取代的C1-C6烷基；z为0或1；A表示可选取代的单环、双环或三环碳环或杂环系统，其中基团R1R2NH-Y-L1-X1-[CH2]Z-和HONHCO-[LINKER]-附着在不同的环原子上；-[Linker]-表示将A中的一个环原子与羟酰胺酸基团CONIIOII连接的二价连接基团，连接基团的长度，从连接到A环原子的末端原子到连接到羟酸胺基团的末端原子，相当于从3-10个碳原子的直链饱和碳氢链的长度。
• PTERIDINE DERIVATIVES AS POLO-LIKE KINASE INHIBITORS USEFUL IN THE TREATMENT OF CANCER
  申请人：Philips Oliver James

  公开号：US20100004250A1

  公开（公告）日：2010-01-07

  Compounds of formula (I) are inhibitors of Polo-like kinases (PLKs), and are useful, inter alia, in the treatment of proliferative diseases: wherein R 1 is hydrogen, or a (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl or (C 3 -C 6 )cycloalkyl group; R 2 is hydrogen, or an optionally substituted (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl or (C 3 -C 6 )cycloalkyl group; R 3 and R 3 ′ are independently selected from hydrogen, —CN, hydroxyl, halogen, optionally substituted (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl or (C 3 -C 6 )cycloalkyl, —NR 6 R 7 or C 1 -C 4 alkoxy, wherein R 6 and R 7 are independently hydrogen or optionally substituted (C 1 -C 6 )alkyl; ring A is an optionally substituted mono- or bi-cyclic carbocyclic or heterocyclic ring or ring system having up to 12 ring atoms; T is a radical of formula (II) R 4 R 5 CH—NH—Y-L 1 -X 1 —  (II) Wherein R 4 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular esterase enzymes to a carboxylic acid group; R 5 is the side chain of a natural or non-natural alpha amino acid; and the linker radical —Y-L 1 -X 1 is as defined in the claims.

  式(I)的化合物是Polo-like激酶(PLKs)的抑制剂，可用于治疗增殖性疾病，其中R1是氢，或(C1-C6)烷基，(C2-C6)烯基，(C2-C6)炔基或(C3-C6)环烷基；R2是氢，或可选取代的(C1-C6)烷基，(C2-C6)烯基，(C2-C6)炔基或(C3-C6)环烷基；R3和R3'分别选自氢，—CN，羟基，卤素，可选取代的(C1-C6)烷基，(C2-C6)烯基，(C2-C6)炔基或(C3-C6)环烷基，—NR6R7或C1-C4烷氧基，其中R6和R7分别是氢或可选取代的(C1-C6)烷基；环A是可选取代的具有最多12个环原子的单环或双环碳环或杂环；T是式(II)的基团R4R5CH—NH—Y-L1-X1—  (II)其中R4是羧酸基(—COOH)，或可被一个或多个细胞内酯酶酶水解为羧酸基的酯基；R5是天然或非天然α氨基酸的侧链；连接基团—Y-L1-X1如权利要求所定义。