ethyl 2-[({[(2-hydroxyethyl)amino]carbonyl}oxy)methyl]-5,7-dimethyl-3-{2-[(methylamino)sulfonyl]phenyl}-4-oxo-3,4-dihydroquinazoline-6-carboxylate | 581106-09-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: ethyl 2-[({[(2-hydroxyethyl)amino]carbonyl}oxy)methyl]-5,7-dimethyl-3-{2-[(methylamino)sulfonyl]phenyl}-4-oxo-3,4-dihydroquinazoline-6-carboxylate
• 英文别名: 2-(2-hydroxy-ethylcarbamoyloxymethyl)-5,7-dimethyl-3-(2-methylsulfamoyl-phenyl)-4-oxo-3,4-dihydro-quinazoline-6-carboxylic acid ethyl ester；ethyl 2-(2-hydroxyethylcarbamoyloxymethyl)-5,7-dimethyl-3-[2-(methylsulfamoyl)phenyl]-4-oxoquinazoline-6-carboxylate
• CAS: 581106-09-4
• 化学式: C₂₄H₂₈N₄O₈S
• 分子量: 532.574
• InChiKey: PMBUDILHPXTDNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  172
• 氢给体数：
  3
• 氢受体数：
  10

制备方法与用途

SAD-448 是一种大麻素受体 1 型（CB1）激动剂，通过作用于周围神经的 CB1 受体来控制痉挛。

反应信息

• 作为反应物：
  描述：

  ethyl 2-[({[(2-hydroxyethyl)amino]carbonyl}oxy)methyl]-5,7-dimethyl-3-{2-[(methylamino)sulfonyl]phenyl}-4-oxo-3,4-dihydroquinazoline-6-carboxylate 在 4-二甲氨基吡啶 、 1,2-二氯乙烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 ethyl 2-((2-(3-aminopropanoyloxy)ethylcarbamoyloxy)methyl)-5,7-dimethyl-3-(2-(N-methylsulfamoyl)phenyl)-4-oxo-3,4-dihydroquinazoline-6-carboxylate
  参考文献：
  名称：

  An Effective Prodrug Strategy to Selectively Enhance Ocular Exposure of a Cannabinoid Receptor (CB_1/2) Agonist

  摘要：

  Glaucoma is a leading cause of vision loss and blindness with increased intraocular pressure (IOP) a prominent risk factor. IOP can be efficaciously reduced by administration of topical agents. However, the repertoire of approved IOP-lowering drug classes is limited, and effective new alternatives are needed. Agonism of the cannabinoid receptor's CB1/2 significantly reduces IOP clinically and experimentally. However, development of CB1/2 agonists has been complicated by the need to avoid cardiovascular and psychotropic side effects. 1 is a potent CB1/2 agonist that is highly excluded from the brain. In a phase I study, compound 1 eyedrops were well tolerated and generated an IOP-lowering trend but were limited in dose and exposure due to poor soluhility and ocular absorption. Here we present an innovative strategy to rapidly identify compound 1 prodrugs that are efficiently metabolized to the parent compound for improved solubility and ocular permeability while maintaining low systemic exposures.

  DOI：

  10.1021/jm4004939
• 作为产物：
  描述：

  2-Hydroxymethyl-5,7-dimethyl-3-(2-methylsulfamoyl-phenyl)-4-oxo-3,4-dihydro-quinazoline-6-carboxylic acid ethyl ester 、 氯甲酸苯酯 、 C.I.酸性橙108 在 氮气 、 乙酸乙酯 、 盐酸 、 Sodium sulfate-III 、 四氢呋喃 、 氩 、 二氯甲烷 、 silica 、 环己烷 作用下， 以 吡啶 为溶剂， 反应 16.75h， 生成 ethyl 2-[({[(2-hydroxyethyl)amino]carbonyl}oxy)methyl]-5,7-dimethyl-3-{2-[(methylamino)sulfonyl]phenyl}-4-oxo-3,4-dihydroquinazoline-6-carboxylate
  参考文献：
  名称：

  Quinazolinone derivatives and their use as cb agonists

  摘要：

  新型喹唑啉衍生物的化学式（I），其中R1-R9如描述中所定义，其生产过程，它们作为药物的用途以及包含它们的药物组合物。

  公开号：

  US20050085493A1

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。
• SYNERGISTIC COMBINATION FOR THE TREATMENT OF PAIN (CANNABINOID RECEPTOR AGONIST AND OPIOID RECEPTOR AGONIST)
  申请人：Adam-Worrall Julia

  公开号：US20090029984A1

  公开（公告）日：2009-01-29

  The invention relates to a pharmaceutical dosage form comprising an analgesic combination for simultaneous or sequential use which comprises a peripherally restricted cannabinoid CB1 receptor agonist having a brain C max to plasma C max ratio of less than 0.1 and an opioid receptor agonist, as well as to a method for treating pain using said pharmaceutical dosage form.

  本发明涉及一种药物剂型，其包括用于同时或顺序使用的镇痛组合物，该组合物包括具有脑Cmax/血浆Cmax比率小于0.1的周围限制性大麻素CB1受体激动剂和阿片受体激动剂，以及使用该药物剂型治疗疼痛的方法。
• Quinazolinone derivatives and their use as CB agonists
  申请人：Brain Thomas Christopher

  公开号：US20070265285A1

  公开（公告）日：2007-11-15

  Novel quinazolinone derivatives of formula I wherein R 1 -R 9 are as defined in the description, processes for their production, their use as pharmaceuticals and pharmaceutical compositions comprising them.

  本发明涉及式I的新型喹唑啉衍生物，其中R1-R9的定义如说明书所述，以及它们的制备方法，它们作为药物的用途以及包含它们的药物组合物。
• 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。
• QUINAZOLINONE DERIVATIVES AND THEIR USE AS CB AGONISTS
  申请人：Novartis AG

  公开号：EP1472234A1

  公开（公告）日：2004-11-03