3-氨基-3-苯并[1,3]二氧戊环-5-基丙酸 | 129042-60-0

• 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
• 中文名称: 3-氨基-3-苯并[1,3]二氧戊环-5-基丙酸
• 英文名称: β-(3,4-methylenedioxyphenyl)-β-alanine
• 英文别名: (+/-)-3-amino-3-benzo[1,3]dioxol-5-ylpropanoic acid；3-amino-3-benzo[1,3]dioxol-5-ylpropionic acid；(S)-3-amino-3-(3,4-methylenedioxyphenyl)propionic acid；3-Amino-3-(Benzo[d]-1,3-dioxolan-5-yl)propionic Acid；3-amino-3-(3,4-methylenedioxyphenyl)propionic acid；3-(benzo[d]dioxolan-5-yl)-3-aminopropionic acid；3-Amino-3-benzo[1,3]dioxol-5-yl-propionsaeure；3-Ammonio-3-(1,3-benzodioxol-5-yl)propanoate；3-azaniumyl-3-(1,3-benzodioxol-5-yl)propanoate
• CAS: 129042-60-0
• 化学式: C₁₀H₁₁NO₄
• mdl: MFCD00736965
• 分子量: 209.202
• InChiKey: DJWMFJZOSZPAHI-UHFFFAOYSA-N

物化性质

• 熔点：
  233 °C (decomp)
• 沸点：
  381.9±42.0 °C(Predicted)
• 密度：
  1.404±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  3-氨基-3-苯并[1,3]二氧戊环-5-基丙酸 在 盐酸 、 lithium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.33h， 生成 β-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-1,3-benzodioxole-5-propanoic acid
  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：

  胡椒醛 在 乙酸铵 、 丙二酸 作用下， 以 乙醇 为溶剂， 生成 3-氨基-3-苯并[1,3]二氧戊环-5-基丙酸
  参考文献：
  名称：

  Heterocyclic anti-epileptogenic agents and methods of use thereof

  摘要：

  本文披露了用于抑制癫痫发生的方法和化合物，例如β-杂环-β-氨基酸。还描述了用于制备和使用本发明的β-杂环-β-氨基酸的方法。

  公开号：

  US20030114441A1

文献信息

• Potent, Orally Active GPIIb/IIIa Antagonists Containing a Nipecotic Acid Subunit. Structure−Activity Studies Leading to the Discovery of RWJ-53308
  作者：William J. Hoekstra、Bruce E. Maryanoff、Bruce P. Damiano、Patricia Andrade-Gordon、Judith H. Cohen、Michael J. Costanzo、Barbara J. Haertlein、Leonard R. Hecker、Becky L. Hulshizer、Jack A. Kauffman、Patricia Keane、David F. McComsey、John A. Mitchell、Lorraine Scott、Rekha D. Shah、Stephen C. Yabut

  DOI：10.1021/jm990418b

  日期：1999.12.1

  intravenously administered antiplatelet fibrinogen receptor (GPIIb/IIIa) antagonists have become established in the acute-care clinical setting for the prevention of thrombosis, orally administered drugs for chronic use are still under development. Herein, we present details from our exploration of structure-activity surrounding the prototype fibrinogen receptor antagonist RWJ-50042 (racemate of 1), which

  尽管在急性护理临床环境中已建立了静脉内施用的抗血小板纤维蛋白原受体（GPIIb / IIIa）拮抗剂，以预防血栓形成，但仍在开发用于长期使用的口服药物。在本文中，我们介绍了围绕原型纤维蛋白原受体拮抗剂RWJ-50042（外消旋体1）的结构活性探索的细节，该结构活性源自涉及纤维蛋白原γ链的独特方法（Hoekstra et al.J.Med。 1995，38，1582）。我们的模拟研究最终发现了有效的口服活性GPIIb / IIIa拮抗剂RWJ-53308（2）。为了从RWJ-50042逐渐发展成为适合临床开发的候选药物，我们进行了一系列优化周期，这些周期采用固相平行合成技术进​​行快速，有效制备了将近250种类似物，对它们的血纤维蛋白原受体亲和力和四种不同激活剂诱导的血小板聚集抑制进行了测定。该策略产生了一些有前途的有希望进行进一步研究的类似物，包括3-（3,4-亚甲二氧基苯）-β-氨基酸类
• Aromatic β-Amino Acids as Asp-Phg Mimics in LDV Derived VLA-4 Antagonists­
  作者：Volkmar Wehner、Horst Blum、Michael Kurz、Hans Stilz

  DOI：10.1055/s-2002-34389

  日期：——

  Aromatic β-amino acid esters 2a-h were prepared in racemic and enantiomerically pure form by the Radionow reaction or based on the method described by Davis and used as mimics of the Asp-Phg C-terminus in LDV derived VLA-4 antagonists. As a promising β-amino acid ester, 11 was identified and used for the synthesis of the highly potent VLA-4 antagonist S9059 with an IC50 of 1.6 nM in a cell attachment assay.

  芳香性 β-氨基酸酯 2a-h 通过 Radionow 反应或基于 Davis 描述的方法制备成外消旋形式和手性纯形式，并作为模拟 LDV 衍生的 VLA-4 拮抗剂中的 Asp-Phg C 末端。作为一种有前景的 β-氨基酸酯，11 被鉴定并用以合成高效力的 VLA-4 拮抗剂 S9059，其在细胞粘附试验中的 IC50 值为 1.6 nM。
• Use of 2,2′-Dibenzothiazolyl Disulfide-Triphenylphosphine and Lawesson’s Reagent in the Cyclization of β-Amino Acids
  作者：Seema Kanwar、S. D. Sharma

  DOI：10.1246/bcsj.79.1748

  日期：2006.11

  The disulfide reagents 2,2'-dithiobisbenzothiazole (MBTS) and 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide (Lawesson's Reagent, LR) mediate the cyclization of /?-amino acids with remarkable product yields. Compared to other cyclodehydrating agents, these have been found to be superior in terms of their cost, making them industrially viable. The advantageous properties of MBTS

  二硫化物试剂 2,2'-二硫代双苯并噻唑 (MBTS) 和 2,4-双(4-甲氧基苯基)-1,3,2,4-二硫代二膦烷 2,4-二硫化物 (Lawesson's Reagent, LR) 介导 /? -具有显着产品产量的氨基酸。与其他环化脱水剂相比，已发现它们在成本方面更胜一筹，使其在工业上可行。MBTS 和 LR 的优势特性使它们成为环脱水剂库中有用且独特的添加剂。
• An efficient new enzymatic method for the preparation of β-aryl-β-amino acid enantiomers
  作者：Gábor Tasnádi、Enikő Forró、Ferenc Fülöp

  DOI：10.1016/j.tetasy.2008.08.009

  日期：2008.9

  An efficient synthesis of β-aryl-β-amino acid enantiomers has been developed via the lipase-catalysed enantioselective hydrolysis of the corresponding racemic ethyl esters in an organic solvent. High enantioselectivities (E >100) were observed when the lipase PS-catalysed reactions were performed with H2O (0.5 equiv) in diisopropyl ether at 45 °C. The products could be easily separated and were obtained

  通过在有机溶剂中通过脂肪酶催化的相应外消旋乙酯的对映选择性水解，已经开发了β-芳基-β-氨基酸对映体的有效合成。当脂肪酶PS催化的H 2 O（0.5当量）在二异丙醚中于45°C进行时，观察到高对映选择性（E > 100）。产物易于分离，收率⩾40％。
• Kinetic resolution of aromatic β-amino acids by ω-transaminase
  作者：Han-Seop Bea、Hye-Jeong Park、Sang-Hyeup Lee、Hyungdon Yun

  DOI：10.1039/c1cc11528f

  日期：——

  Racemic aromatic β-amino acids have been kinetically resolved into (R)-β-amino acids with high enantiomeric excess (>99%) by a novel ω-TA with ca. 50% conversion.

  手性芳香β-氨基酸通过一种新型的ω-转氨酶被动能分离为高对映体过剩的(R)-β-氨基酸，转化率约为50%。