4-(2-Trimethylsilylethynyl)-2-azetidinone | 153248-41-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 4-(2-Trimethylsilylethynyl)-2-azetidinone
• 英文别名: 4-(2-trimethylsilylethynyl)azetidin-2-one
• CAS: 153248-41-0
• 化学式: C₈H₁₃NOSi
• 分子量: 167.283
• InChiKey: LQGSFHVFEMXYAD-UHFFFAOYSA-N

物化性质

• 沸点：
  258.8±29.0 °C(Predicted)
• 密度：
  1.00±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.76
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-(2-Trimethylsilylethynyl)-2-azetidinone 在 Lipase PS(R) 作用下， 以 二氯甲烷 、 异丙醚 为溶剂， 反应 16.0h， 生成 (4S)-1-(hydroxymethyl)-4-(2-trimethylsilylethynyl)azetidin-2-one
  参考文献：
  名称：

  An efficient synthesis of the orally-active GpIIb/IIIa antagonist FR184764

  摘要：

  An efficient synthesis of the orally-active GpIIb/IIIa antagonist FR184764 was achieved. The key intermediate, an optically active ethynyl beta-amino ester, was synthesized efficiently by utilizing a lipase catalyzed kinetic resolution step. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2004.01.157
• 作为产物：
  描述：

  4-乙酰氧基-2-氮杂环丁酮 、 magnesium,ethynyl(trimethyl)silane,bromide 反应 2.0h， 以100%的产率得到4-(2-Trimethylsilylethynyl)-2-azetidinone
  参考文献：
  名称：

  An efficient synthesis of the orally-active GpIIb/IIIa antagonist FR184764

  摘要：

  An efficient synthesis of the orally-active GpIIb/IIIa antagonist FR184764 was achieved. The key intermediate, an optically active ethynyl beta-amino ester, was synthesized efficiently by utilizing a lipase catalyzed kinetic resolution step. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2004.01.157

文献信息

• Design, synthesis and biological activity of novel enediynyl monocyclic β-lactams
  作者：Amit Basak、Uttam Kumar Khamrai

  DOI：10.1016/0040-4039(96)00297-3

  日期：1996.4

  Monocyclic β-lactams 1–3 substituted at C-4 with enediyne moiety have been synthesized via Pd(0) mediated coupling reaction. Their antibacterial activity against ampicillin-resistant E. coli have been tested.

  通过Pd（0）介导的偶联反应合成了在C-4处被烯二炔部分取代的单环β-内酰胺1-3。已经测试了它们对耐氨苄青霉素的大肠杆菌的抗菌活性。
• Substituted .beta.-amino acid derivatives useful as platelet aggregation
  申请人：Monsanto Company

  公开号：US05239113A1

  公开（公告）日：1993-08-24

  Novel substituted .beta. amino acid derivatives are provided which inhibit platelet aggregation and intermediates thereof. This invention also pertains to pharmaceutical compositions and methods of using such derivatives.

  本发明提供了一种替代的新型.beta.氨基酸衍生物，能够抑制血小板聚集，以及其中间体。本发明还涉及制备这些衍生物的药物组合物和使用这些衍生物的方法。
• Beta-alanine derivative and a process for the preparation thereof
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：US20010051730A1

  公开（公告）日：2001-12-13

  This invention relates to &bgr;-alanine derivatives represented by the following formula: 1 wherein each symbol is as defined in the specification and pharmaceutically acceptable salt thereof which is glycoprotein IIb/IIIa antagonist, inhibitor of blood platelets aggregation and inhibitor of the binding of fibrinogen to blood platelets, to processes for the preparation thereof, to a pharmaceutical composition comprising the same and to a method for the prevention and/or treatment diseases indicated in the specification to a human being or an animal.

  本发明涉及以下式子所代表的β-丙氨酸衍生物：1其中每个符号如规范中定义的药学上可接受的盐是糖蛋白IIb/IIIa拮抗剂，血小板聚集抑制剂和纤维蛋白原与血小板结合的抑制剂，以及其制备方法，包括该化合物的制药组合物和用于预防和/或治疗规范中指示的人类或动物疾病的方法。
• Potent in Vitro and in Vivo Inhibitors of Platelet Aggregation Based Upon the Arg-Gly-Asp Sequence of Fibrinogen. (Aminobenzamidino)succinyl (ABAS) Series of Orally Active Fibrinogen Receptor Antagonists
  作者：Jeffery A. Zablocki、Joseph G. Rico、Robert B. Garland、Thomas E. Rogers、Kenneth Williams、Lori A. Schretzman、Shashidhar A. Rao、Philippe R. Bovy、Foe S. Tjoeng

  DOI：10.1021/jm00013a014

  日期：1995.6

  Our initial orally active fibrinogen receptor antagonist benzamidinopentanoyl (BAP) series which was discovered through truncation of our iv antiplatelet agent (SC-52012) demonstrated modest oral activity in canine studies (ethyl [5-(4-amidinophenyl)pentanoyl]3-3-amino-3 pyridyl)propionate, 1e). Introduction of an amide bond adjacent to the benzamidine led to a novel series with an (aminobenzamidino)succinyl (ABAS) Arg-Gly surrogate that had improved in vitro potency (5-17 times) relative to the BAP series. Four ester prodrug/acid active metabolite pairs (2a/2e, 60a/60e, 62a/62e, 63a/63e) from the ABAS series which varied in their 3-substituent on the beta-amino ester ''aspartate mimetic'' were prepared in enantiomerically enriched form (>95:5), and they were evaluated in canine studies for their ability to block collagen-induced aggregation in platelet-rich plasma, the elimination profile (t(1/2) beta-phase), repeated oral dosing studies, and oral systemic availability. Of the four ester prodrug/acid active metabolite pairs, 2e/2a (SC-54684A/SC-54701A) had the most favorable properties in the above studies with an IC50 = 67 +/- 5 nM (dog platelet-rich plasma, collagen), t(1/2) beta = 1.6 h tester) and 6.5 h (acid), no adverse effects upon repeated dosing, and a drug oral systemic availability of 62% (area under curve (AUG) of acid 2a (drug) following ig administration of ester 2e (prodrug, 2.5 mg/kg) divided by AUC of acid 2a (drug) following iv administration of ester 2e (prodrug, 2.5 mg/kg) as determined by HPLRC). In further pharmacokinetic studies using nonlabeled 2e/2a, the oral systemic availability tester 2e ig/ester 2e iv) of 2e was measured to be in the range of 44.7-53.0%. The more biologically relevant oral systemic availability tester 2e ig/acid 2a iv) of 2e was found to be in the range of 22.0-26.4%. A pharmacophore model. based on inhibitors from several different benzamidine classes including 2a (ABAS class) was developed using a combination of molecular modeling (MM2) and pharmacophore identification (APOLLO) methods.
• J. Med. Chem. 1995, 38, 2378-2394
  作者：

  DOI：——

  日期：——