O²-ethyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: O²-ethyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate
• 英文别名: (Z)-ethoxyimino-oxido-pyrrolidin-1-ylazanium
• 化学式: C₆H₁₃N₃O₂
• 分子量: 159.188
• InChiKey: WSEVUUHCTCVKLI-CLFYSBASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  53.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  硫酸二乙酯 、 sodium 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate 在 sodium carbonate 作用下， 以 甲醇 为溶剂， 以40%的产率得到O²-ethyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  Targeting Nitric Oxide (NO) Delivery in Vivo. Design of a Liver-Selective NO Donor Prodrug That Blocks Tumor Necrosis Factor-α-Induced Apoptosis and Toxicity in the Liver

  摘要：

  We have designed a drug that protects the liver from apoptotic cell death by organ-selective pharmacological generation of the bioregulatory agent, nitric oxide (NO). The discovery strategy involved three steps: identifying a diazeniumdiolate ion (R2N[N(O)NO](-), where R2N = pyrrolidinyl) that spontaneously decomposes to NO with a very short half-life (3 s) at physiological pH; converting this ion to a series of potential prodrug derivatives by covalent attachment of protecting groups that we postulated might be rapidly removed by enzymes prevalent in the liver; and screening the prodrug candidates in vitro and in vivo to select a lead and to confirm the desired activity. Of five cell types examined, only cultured hepatocytes metabolized O-2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO) to NO, triggering cyclic guanosine 3',5'-monophosphate (cGMP) synthesis and protecting the hepatocytes from apoptotic cell death induced by treatment with tumor necrosis factor-alpha (TNF alpha) plus actinomycin D. In vivo, V-PYRRO/NO increased Liver cGMP levels while minimally affecting systemic hemodynamics, protecting rats dosed with TNF alpha plus galactosamine from apoptosis and hepatotoxicity. The results illustrate the potential utility of diazeniumdiolates for targeting NO delivery in vivo and suggest a possible therapeutic strategy for hepatic disorders such as fulminant liver failure.

  DOI：

  10.1021/jm9701031

文献信息

• PROSTAGLANDIN CONJUGATES AND DERIVATIVES FOR TREATING GLAUCOMA AND OCULAR HYPERTENSION
  申请人：NOVARTIS AG

  公开号：US20160108012A1

  公开（公告）日：2016-04-21

  Prostaglandin conjugates and derivatives and methods for their use to treat glaucoma and/or lower intraocular pressure are disclosed. Additionally, ophthalmic pharmaceutical compositions useful in the treatment of eye diseases such as glaucoma and elevated intraocular pressure are disclosed. Such compositions comprise an effective amount of prostaglandin conjugates or derivatives of the present invention.

  本发明公开了用于治疗青光眼和/或降低眼内压的前列腺素共轭物和衍生物以及其使用方法。此外，本发明还公开了用于治疗眼部疾病如青光眼和眼内压升高的眼科药物组合物。这些组合物包括本发明的前列腺素共轭物或衍生物的有效量。
• NSAIDs DERIVATIVES AND USES THEREOF
  申请人：THE RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK

  公开号：US20150376162A1

  公开（公告）日：2015-12-31

  The present invention discloses novel compounds derived from NSAIDs and pharmaceutically acceptable salts thereof. Other aspects of the invention relate to use of the NSAID derivatives in treating inflammatory diseases and pharmaceutical compositions thereof.

  本发明揭示了从非甾体抗炎药（NSAIDs）衍生出的新化合物及其药学上可接受的盐。本发明的其他方面涉及使用NSAID衍生物治疗炎症性疾病以及其制药组合物。
• Prostaglandin conjugates and derivatives for treating glaucoma and ocular hypertension
  申请人：Novartis AG

  公开号：US10016441B2

  公开（公告）日：2018-07-10

  Prostaglandin conjugates and derivatives and methods for their use to treat glaucoma and/or lower intraocular pressure are disclosed. Additionally, ophthalmic pharmaceutical compositions useful in the treatment of eye diseases such as glaucoma and elevated intraocular pressure are disclosed. Such compositions comprise an effective amount of prostaglandin conjugates or derivatives of the present invention.

  本研究公开了前列腺素轭合物和衍生物及其用于治疗青光眼和/或降低眼内压的方法。此外，还公开了用于治疗青光眼和眼压升高等眼科疾病的眼科药物组合物。此类组合物包含有效量的本发明前列腺素共轭物或衍生物。
• COMPOSITIONS AND METHODS FOR TREATING OR PREVENTING METABOLIC SYNDROME DISORDERS
  申请人：CHARLES DREW UNIVERSITY OF MEDICINE AND SCIENCE

  公开号：US20160120890A1

  公开（公告）日：2016-05-05

  The invention provides methods, compositions, uses of compositions, assays and kits for modulating brown adipose tissue (BAT) in animals and patients with obesity, insulin resistance and perturbed glucose homeostasis are disclosed. Accordingly, methods, compositions, uses of compositions, and kits are useful for the amelioration of pathological conditions characterized by storage of excess energy, insulin resistance and related metabolic syndromes often associated with obesity.
• Method of Priming Plants Against Abiotic Stress Factors
  申请人：Research Foundation of the City University of New York

  公开号：US20170174651A1

  公开（公告）日：2017-06-22

  A method of reducing cellular damage to a plant by treating the plant with a compound containing an NO-releasing moiety and an H 2 S-releasing moiety covalently bonded to an aspirin derived core or a NOSH compound is claimed. The compounds may also be used in a method of priming a plant against abiotic stress factors and a method of promoting plant growth.