L-methionine isopropyl ester | 49550-09-6

• 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: L-methionine isopropyl ester
• 英文别名: propan-2-yl (2S)-2-amino-4-methylsulfanylbutanoate
• CAS: 49550-09-6
• 化学式: C₈H₁₇NO₂S
• 分子量: 191.294
• InChiKey: WLUAUPQSKOQURS-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  77.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  L-methionine isopropyl ester 、 2-(4-甲基萘-1-基)-4-硝基苯甲酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以89%的产率得到
  参考文献：
  名称：

  Farnesyltransferase inhibitors: CAAX mimetics based on different biaryl scaffolds

  摘要：

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed as farnesyltransferase (FTase) inhibitors (FTIs) by replacing AA with o-aryl or o-heteroaryl substituted p-hydroxy- or p-aminobenzoic acid, while maintaining the replacement of C with 1,4-benzodioxan-2-ylmethyl or 2-amino-4-thiazoly-lacetyl residue as in previous CAAX mimetics. Both FTase inhibition and antiproliferative effect were showed by two thiazole derivatives, namely those with 1-naphthyl (10 and 10a) or 3-furanyl (15 and 15a) in the central spacer, and by the benzodioxane derivative with 2-thienyl (6 and 6a) in the same position. Accumulation of unprenylated RAS was demonstrated in cells incubated with 15a. Consistently with FTIs literature, such results delineate the biaryl scaffold not only as a spacer but also as a sensible area of these mimetic molecules, where modifications at the branching aromatic ring are not indifferent and should be matter of further investigation. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.078
• 作为产物：
  描述：

  N,N-Diallyl-L-methionine isopropyl ester 在 四(三苯基膦)钯 1,3-二甲基巴比妥酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 L-methionine isopropyl ester
  参考文献：
  名称：

  Mild and selective palladium(0)-catalyzed deallylation of allylic amines. Allylamine and diallylamine as very convenient ammonia equivalents for the synthesis of primary amines

  摘要：

  DOI：

  10.1021/jo00074a044

文献信息

• SUBSTITUTED NUCLEOTIDE ANALOGS
  申请人：ALIOS BIOPHARMA, INC.

  公开号：US20130164261A1

  公开（公告）日：2013-06-27

  Disclosed herein are phosphorothioate nucleotide analogs, methods of synthesizing phosphorothioate nucleotide analogs and methods of treating diseases and/or conditions such as viral infections, cancer, and/or parasitic diseases with the phosphorothioate nucleotide analogs.

  本文披露了磷硫酸酯核苷类似物，合成磷硫酸酯核苷类似物的方法，以及利用磷硫酸酯核苷类似物治疗病毒感染、癌症和/或寄生虫病等疾病和/或症状的方法。
• Inhibitors of protein isoprenyl transferases
  申请人：University of Pittsburgh

  公开号：US20020193596A1

  公开（公告）日：2002-12-19

  Compounds having the formula 1 or a pharmaceutically acceptable salt thereof wherein R 1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L 2 —, and (i) heterocyclic-L 2 —; R 2 is selected from (a) 2 (b) —C(O)NH—CH(R 14 )—C(O)OR 15 , (c) 3 (d) —C(O)NH—CH(R 14 )—C(O)NHSO 2 R 16 (e) —C(O)NH—CH(R 14 )-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R 14 )—C(O)NR 17 R 18 ; R 3 is heterocyclic, aryl, substituted or unsubstituted cycloalkyl; R 4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L 1 is absent or is selected from (a) —L 4 —N(R 5 )—L 5 —, (b) —L 4 —O—L 5 —, (c) —L 4 —S(O) n —L 5 — (d) —L 4 -L 6 —C(W)—N(R 5 )—L 5 —, (e) —L 4 -L 6 —S(O) m —N(R 5 )—L 5 —, (f) —L 4 —N(R 5 )—C(W)—L 7 -L 5 —, (g) —L 4 —N(R 5 )—S(O) p —L 7 —L 5 —, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, and (j) optionally substituted alkynylene are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.

  具有以下公式的化合物或其药学上可接受的盐，其中R1为(a)氢，(b)较低的烷基，(c)烯基，(d)烷氧基，(e)硫代烷氧基，(f)卤素，(g)卤代烷基，(h)芳基-L2—，以及(i)杂环-L2—；R2从(a)中选择，(b) -C(O)NH-CH(R14)-C(O)OR15，(c)中选择，(d) -C(O)NH-CH(R14)-C(O)NHSO2R16，(e) -C(O)NH-CH(R14)-四唑基，(f) -C(O)NH-杂环，以及(g) -C(O)NH-CH(R14)-C(O)NR17R18；R3为杂环，芳基，取代或未取代的环烷基；R4为氢，较低烷基，卤代烷基，卤素，芳基，芳基烷基，杂环基，或(杂环)烷基；L1为空缺或从(a) -L4-N(R5)-L5-，(b) -L4-O-L5-，(c) -L4-S(O)n-L5-，(d) -L4-L6-C(W)-N(R5)-L5-，(e) -L4-L6-S(O)m-N(R5)-L5-，(f) -L4-N(R5)-C(W)-L7-L5-，(g) -L4-N(R5)-S(O)p-L7-L5-，(h)可选择取代的烷基，(i)可选择取代的烯基，以及(j)可选择取代的炔基是蛋白异戊二烯转移酶的抑制剂。还公开了蛋白异戊二烯转移酶抑制组合物和抑制蛋白异戊二烯转移酶的方法。
• 3-Mercaptopyrrolidines as farnesyl protein transferase inhibitors
  申请人：Boyle Thomas Francis

  公开号：US20050209217A1

  公开（公告）日：2005-09-22

  The present invention relats to inhibitors of ras farnesylation of Formula (I) wherein: R 1 is for example H and further values as defined in the specification; R 2 is for example H and further values as defined in the specification; R 3 is for example H or a substituent having values as defined in the specification; p is 0-3 in which R 3 values can be the same or different; L is a linking moiety for example —CH 2 —NH— and further values as defined in the specification; A is selected from phenyl; naphthyl; a 5-10 membered monocyclic or bicyclic heteroaryl ring containing up to 5 heteroatoms where the heteroatoms are independently selected from O, N and S; or a —S—S— dimer thereof when R 2 =H; or a N-oxide or a pharmaceutically-acceptable salt, prodrug or solvate thereof. Processes for their preparation, their use as therapeutic agents and pharmaceutical compositions containing them. A particular use is in cancer therapy.

  本发明涉及 Formula (I) 的 ras 泛酰化抑制剂，其中：R1 例如为 H，以及在规范中定义的进一步数值；R2 例如为 H，以及在规范中定义的进一步数值；R3 例如为 H 或具有在规范中定义的数值的取代基；p 为 0-3，其中 R3 的数值可以相同也可以不同；L 是一个连接基团，例如 —CH2—NH—，以及在规范中定义的进一步数值；A 选自苯基；萘基；一个含有最多 5 个杂原子的 5-10 成员单环或双环杂芳基环，其中杂原子独立地选自 O、N 和 S；或者当 R2=H 时的一个 —S—S— 二聚体；或者其 N-氧化物或药用可接受的盐、前药或溶剂。它们的制备方法，作为治疗剂的用途以及含有它们的药物组合物。一个特定用途是在癌症治疗中。
• Inhibitors of farnesyl protein transferase
  申请人：——

  公开号：US20030096842A1

  公开（公告）日：2003-05-22

  This invention relates to compounds of formula (I) that inhibit farnesylation of gene products through inhibition of the enzyme farnesyl-protein transferase (FPTase). The invention also relates to methods of manufacturing the compounds, pharmaceutical compositions and methods of treating diseases, especially cancer, which are mediated through farnesylation.

  这项发明涉及公式（I）的化合物，通过抑制酶法尼基-蛋白质转移酶（FPTase）来抑制基因产物的法尼酰化。该发明还涉及制造这些化合物的方法、药物组合物以及治疗疾病的方法，特别是通过法尼酰化介导的癌症。
• Application of an Enantiomerically Pure Bicyclic Thiolactone in the Synthesis of a Farnesyl Transferase Inhibitor
  作者：Sahar Abbas、Leigh Ferris、Alison K. Norton、Lyn Powell、Graham E. Robinson、Paul Siedlecki、Rebecca J. Southworth、Andrew Stark、Emyr G. Williams

  DOI：10.1021/op700218j

  日期：2008.3.1

  operated successfully and reproducibly on the large scale. Removal of an N-Boc protecting group in the final step of the drug synthesis required careful choice of conditions to avoid cleaving other ester groups in the molecule. An impurity formed in the deprotection step was identified as the S- tert-butyl analogue arising from attack of the tert-butyl cation on the methionine residue; its identity was confirmed

  描述了一种新颖的法呢基转移酶抑制剂的有效生产途径。靶分子是前药，并且由于不稳定的功能性的存在，其合成变得复杂。药物化学合成需要三苯甲基硫醇立体定向地引入巯基。新途径的重要目标是避免这种原子效率低的保护基，这是通过使用双环硫代内酯实现的。用DIBAL还原硫代内酯可得到掩蔽的醛，该醛可干净地参与关键的还原胺化步骤，而不会损失立体化学完整性。发现所报道的制备硫代内酯的方法产生不一致的结果。开发工作导致了一个伸缩过程，该过程成功且可重复地大规模运行。在药物合成的最后步骤中要去除N-Boc保护基，需要仔细选择条件，以避免分子中其他酯基的裂解。在脱保护步骤中形成的杂质被鉴定为S-由于叔丁基阳离子攻击蛋氨酸残基而产生的叔丁基类似物 ；通过独立合成证实了其身份。