ethyl 3-amino-(3S)-ethynylpropionate hydrochloride | 149251-15-0

• 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: ethyl 3-amino-(3S)-ethynylpropionate hydrochloride
• 英文别名: ethyl 3(S)-3-aminopent-4-ynoate；(S)-ethyl 3-amino-4-pentynoate；(S)-ethyl 3-aminopent-4-ynoate；ethyl 3(S)-amino-4-pentynoate；ethyl (3S)-3-aminopent-4-ynoate
• CAS: 149251-15-0
• 化学式: C₇H₁₁NO₂
• 分子量: 141.17
• InChiKey: XDCFZUJTBDNKAT-ZCFIWIBFSA-N

物化性质

• 沸点：
  214.8±30.0 °C(Predicted)
• 密度：
  1.042±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 3-amino-(3S)-ethynylpropionate hydrochloride 在 4-二甲氨基吡啶 、 硫酸氢铵 、 phosphate buffer 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 SC-54701
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00013a014
• 作为产物：
  描述：

  ethyl (S)-3-amino-5-(trimethylsilyl)-4-pentynoate 在 四丁基氟化铵 作用下， 生成 ethyl 3-amino-(3S)-ethynylpropionate hydrochloride
  参考文献：
  名称：

  A very short, efficient and inexpensive synthesis of the prodrug form of SC-54701A a platelet aggregation inhibitor

  摘要：

  A short and efficient synthesis of the prodrug form of SC-54701A has been achieved from (trimethylsilyl)acetylene in 6 steps with an overall yield of 19%. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00293-x

文献信息

• Nonpeptide αvβ3 antagonists. Part 2: constrained glycyl amides derived from the RGD tripeptide
  作者：Robert S. Meissner、James J. Perkins、Le T. Duong、George D. Hartman、William F. Hoffman、Joel R. Huff、Nathan C. Ihle、Chih-Tai Leu、Rose M. Nagy、Adel Naylor-Olsen、Gideon A. Rodan、Sevgi B. Rodan、David B. Whitman、Gregg A. Wesolowski、Mark E. Duggan

  DOI：10.1016/s0960-894x(01)00687-4

  日期：2002.1

  the RGD tripeptide are described that are potent, selective antagonists of the integrin receptor, alpha(v)beta(3). The use of the 5,6,7,8-tetrahydro[1,8]naphthyridine group as a potency-enhancing N-terminus is demonstrated. Two 3-substituted-3-amino-propionic acids previously contained in alpha(IIb)beta(3) antagonists were utilized to enhance binding affinity and functional activity for the targeted

  描述了RGD三肽的模拟物，它们是整联蛋白受体α（v）beta（3）的有效选择性拮抗剂。证明了使用5,6,7,8-四氢[1,8]萘啶基作为增强效价的N-末端。以前包含在alpha（IIb）beta（3）拮抗剂中的两个3-取代的-3-氨基丙酸被用来增强对目标受体的结合亲和力和功能活性。然后，通过使用环状缩水甘油酰胺键约束，进一步提高了亲和力。
• [EN] INHIBITORS OF CREATINE TRANSPORT AND USES THEREOF<br/>[FR] INHIBITEURS DE TRANSPORT DE CRÉATINE ET LEURS UTILISATIONS
  申请人：RGENIX INC

  公开号：WO2016176636A1

  公开（公告）日：2016-11-03

  This invention relates to compounds that inhibit creatine transport and/or creatine kinase, pharmaceutical compositions including such compounds, and methods of utilizing such compounds and compositions for the treatment of cancer.

  这项发明涉及抑制肌酸转运和/或肌酸激酶的化合物，包括这些化合物的药物组合物，以及利用这些化合物和组合物治疗癌症的方法。
• [EN] INHIBITORS OF CREATINE TRANSPORT AND USES THEREOF<br/>[FR] INHIBITEURS DE TRANSPORT DE LA CRÉATINE ET LEURS UTILISATIONS
  申请人：RGENIX INC

  公开号：WO2015168465A1

  公开（公告）日：2015-11-05

  This invention relates to compounds that inhibit creatine transport and/or creatine kinase, pharmaceutical compositions including such compounds, and methods of utilizing such compounds and compositions for the treatment of cancer.

  这项发明涉及抑制肌酸转运和/或肌酸激酶的化合物，包括这种化合物的药物组合物，以及利用这种化合物和组合物治疗癌症的方法。
• Platelet aggregation inhibitors
  申请人：G. D. Searle & Co

  公开号：US05721366A1

  公开（公告）日：1998-02-24

  This invention relates to compounds having the following formula ##STR1## or a pharmaceutically acceptable salt thereof which are useful in the inhibition of platelet aggregation, to pharmaceutical compositions of such phenylamidines derivatives, and to a method of inhibiting platelet aggregation in mammals by administering such compounds and compositions.

  这项发明涉及具有以下结构式的化合物##STR1##或其药用可接受盐，这些化合物对抑制血小板聚集具有用处，以及这些苯基酰胺衍生物的药物组合物，以及通过给予这些化合物和组合物来抑制哺乳动物的血小板聚集的方法。
• A two-step, one-pot procedure using acid chlorides and propargyl amines to form tri-substituted oxazoles via gold-catalyzed cyclization
  作者：Michelle Tran-Dubé、Sarah Johnson、Indrawan McAlpine

  DOI：10.1016/j.tetlet.2012.11.013

  日期：2013.1

  2,4-Disubstituted-5-methyl oxazoles were prepared from a 2-step, 1-pot procedure using acid chlorides and propargyl amines. These conditions lead to the formation of propargyl amides in situ followed by AuCl3 catalyzed cyclization. We were interested in this novel formation of tri-substituted oxazoles and exploring the scope of the reaction using these mild conditions. A variety of aryl and aliphatic

  使用酰基氯和炔丙基胺，通过两步，一锅法制备2,4-二取代的5-甲基恶唑。这些条件导致原位形成炔丙基酰胺，然后AuCl 3催化环化。我们对这种新型的三取代恶唑的形成感兴趣，并探索了在这些温和条件下的反应范围。耐受各种含有敏感官能团的芳基和脂族酰胺，可提供良好的收率。