Propanoic acid 2,2,2-trichloroethyl ester | 84443-43-6

• 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: Propanoic acid 2,2,2-trichloroethyl ester
• 英文别名: 2,2,2-trichloroethyl propionate；trichloroethyl propionate；2,2,2-trichloroethyl propanoate
• CAS: 84443-43-6
• 化学式: C₅H₇Cl₃O₂
• 分子量: 205.468
• InChiKey: MEFWWUOADZDECZ-UHFFFAOYSA-N

物化性质

• 保留指数：
  1087;1078;1080;1089;1094;1101;1057

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Propanoic acid 2,2,2-trichloroethyl ester 、 反应 1.0h， 生成 [(2R,3S,4S,5R)-4-hydroxy-5-(6-methoxypurin-9-yl)-3-propanoyloxyoxolan-2-yl]methyl propanoate
  参考文献：
  名称：

  Di- and triester prodrugs of the varicella-zoster antiviral agent 6-methoxypurine arabinoside

  摘要：

  6-Methoxypurine arabinoside (9-beta-D-arabinofuranosyl-6-methoxy-9H-purine, 1) has potent and selective activity against varicella-zoster virus in vitro. An unfavorable metabolic profile observed with oral dosing in the rat led to the preparation of a variety of 2',3',5'-triesters (2a-n) and several 2',3'-, 2',5'-, and 3',5-diester, of this arabinoside (3a-n, 4a-f, and 5a-j, respectively). The compounds were evaluated as prodrugs by measuring the urinary levels of 1 in rat urine after oral dosing. With the exception of triacetate 2a, the triesters failed to significantly enhance bioavailability. Administration of compound 2a resulted in a 3-fold increase in systemic availability of 1, possibly because of its increased water solubility (1.6 times more soluble than 1) and only slightly increased relative log P value (1.93 vs 0.50 for 1). The longer chain aliphatic triesters and aromatic triesters had lower water solubilities and increased lipophilic partitioning. These factors might account for the lower systemic bioavailability of these compounds. In contrast, the diesters, especially the aliphatic diesters, showed significantly improved systemic availability. This might be a consequence of the higher aqueous solubilities and enhanced partition coefficients seen with these compounds. 2',3-Diacetate 3a showed the best combination of high systemic availability and water solubility of all the prodrugs of 1.

  DOI：

  10.1021/jm00079a006
• 作为产物：
  描述：

  2,2,2-三氯乙醇 、 丙酰氯 在 吡啶 作用下， 生成 Propanoic acid 2,2,2-trichloroethyl ester
  参考文献：
  名称：

  Di- and triester prodrugs of the varicella-zoster antiviral agent 6-methoxypurine arabinoside

  摘要：

  6-Methoxypurine arabinoside (9-beta-D-arabinofuranosyl-6-methoxy-9H-purine, 1) has potent and selective activity against varicella-zoster virus in vitro. An unfavorable metabolic profile observed with oral dosing in the rat led to the preparation of a variety of 2',3',5'-triesters (2a-n) and several 2',3'-, 2',5'-, and 3',5-diester, of this arabinoside (3a-n, 4a-f, and 5a-j, respectively). The compounds were evaluated as prodrugs by measuring the urinary levels of 1 in rat urine after oral dosing. With the exception of triacetate 2a, the triesters failed to significantly enhance bioavailability. Administration of compound 2a resulted in a 3-fold increase in systemic availability of 1, possibly because of its increased water solubility (1.6 times more soluble than 1) and only slightly increased relative log P value (1.93 vs 0.50 for 1). The longer chain aliphatic triesters and aromatic triesters had lower water solubilities and increased lipophilic partitioning. These factors might account for the lower systemic bioavailability of these compounds. In contrast, the diesters, especially the aliphatic diesters, showed significantly improved systemic availability. This might be a consequence of the higher aqueous solubilities and enhanced partition coefficients seen with these compounds. 2',3-Diacetate 3a showed the best combination of high systemic availability and water solubility of all the prodrugs of 1.

  DOI：

  10.1021/jm00079a006

文献信息

• [EN] TRICYCLIC DEGRADERS OF IKAROS AND AIOLOS<br/>[FR] AGENTS DE DÉGRADATION TRICYCLIQUES D'IKAROS ET D'AIOLOS
  申请人：C4 THERAPEUTICS INC

  公开号：WO2020210630A1

  公开（公告）日：2020-10-15

  Tricyclic cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway for therapeutic applications are described.

  三环脑蛋白结合剂通过泛素蛋白酶体途径降解Ikaros或Aiolos以用于治疗应用的描述。
• KRAS G12C INHIBITORS AND METHODS OF USING THE SAME
  申请人：Amgen Inc.

  公开号：US20210009577A1

  公开（公告）日：2021-01-14

  Provided herein are KRAS G12C inhibitors, composition of the same, and methods of using the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.

  本文提供KRAS G12C抑制剂，其组成，以及使用方法。这些抑制剂对于治疗多种疾病有用，包括胰腺癌，结直肠癌和肺癌。
• 9-.beta.-D-arabinofuranasyl-2-amino-6-methaoxy-9H-purine
  申请人：Burroughs Wellcome Co.

  公开号：US05424295A1

  公开（公告）日：1995-06-13

  The compound 9-B-D-arabinofuranosyl-2-amino-6-methoxy-9H-purine along with its 5'-acetyl and 5'-(4-methoxy-4-oxobutyryl derivatives are disclosed as inhibitors of Varicella Zoster virus (VZV).

  化合物9-B-D-阿拉伯糖呋喃基-2-氨基-6-甲氧基-9H-嘌呤及其5'-乙酰基和5'-(4-甲氧基-4-氧代丁酰基)衍生物被披露为水痘-带状疱疹病毒（VZV）的抑制剂。
• Methods of treating alzheimer's disease
  申请人：Schostarez Heinrich

  公开号：US20050130941A1

  公开（公告）日：2005-06-16

  Disclosed are methods for treating Alzheimer's disease, and other diseases, and/or inhibiting beta-secretase enzyme, and/or inhibiting deposition of A beta peptide in a mammal, by use of hydrazine compounds of formula (I) wherein the variables R 1 -R 9 are defined herein.

  本发明涉及使用式(I)中变量R1-R9所定义的肼化合物治疗阿尔茨海默病和其他疾病，抑制β-分泌酶酶活性，抑制A beta肽在哺乳动物体内的沉积。
• Method for treating T-cell lymphoblastic leukemia with ara-G nucleoside
  申请人：Burroughs Wellcome Co. (141)

  公开号：US05492897A1

  公开（公告）日：1996-02-20

  6-Alkoxy derivatives of Ara-G, and pharmaceutically acceptable esters thereof, are described as being useful in tumor therapy. Novel pharmaceutically acceptable esters, their preparation and pharmaceutical formulations containing them are also disclosed.

  本文描述了Ara-G的6-烷氧基衍生物及其药学上可接受的酯类，被认为在肿瘤治疗中有用。还披露了新型药学上可接受的酯类，它们的制备以及含有它们的制药配方。