3,3-dimethyl-4-(2'-phenylethyl)azetidin-2-one | 180181-47-9

• 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: 3,3-dimethyl-4-(2'-phenylethyl)azetidin-2-one
• 英文别名: 4-phenethyl-3,3-dimethyl-2-azetidinone；3,3-Dimethyl-4-(2-phenylethyl)azetidin-2-one
• CAS: 180181-47-9
• 化学式: C₁₃H₁₇NO
• 分子量: 203.284
• InChiKey: HCVKIJMGMIDCSD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 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：

  3,3-dimethyl-4-(2'-phenylethyl)azetidin-2-one 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 1-(hydroxymethyl)-3,3-dimethyl-4-(2-phenylethyl)azetidin-2-one
  参考文献：
  名称：

  Convenient Syntheses of Optically Active .BETA.-Lactams by Enzymatic Resolution.

  摘要：

  通过脂肪酶催化的动力学分辨，合成了光学活性的β-内酰胺，利用N-酰氧甲基β-内酰胺（3）在有机溶剂中的对映选择性水解以及N-羟甲基β-内酰胺（2）与乙烯基醋酸酯的转酯化反应。获得了多种在3、4位或两者位置具有一些取代基的高光学纯度的β-内酰胺（2和3），所制备的光学活性的N-羟甲基β-内酰胺在不发生消旋化的情况下转化为有用的N-无取代基的形式。

  DOI：

  10.1248/cpb.41.1933
• 作为产物：
  描述：

  1-benzoylamino-3,3-dimethyl-4-(2'-phenylethyl)azetidin-2-one 在 甲醇 、 六甲基磷酰三胺 、 samarium diiodide 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 以67%的产率得到3,3-dimethyl-4-(2'-phenylethyl)azetidin-2-one
  参考文献：
  名称：

  Mannich Type Reactions of Acylhydrazones with Silyl Enolates for the Synthesis of b-Amino Ester, b-Amino Ketone, b-Lactam, Pyrazolidinone, and Pyrazolone Derivatives

  摘要：

  DOI：

  10.3987/com-99-s113

文献信息

• <i>N</i>-[2,2-Dimethyl-3-(<i>N</i>-(4-cyanobenzoyl)amino)nonanoyl]-<scp>l</scp>-phenylalanine Ethyl Ester as a Stable Ester-Type Inhibitor of Chymotrypsin-like Serine Proteases:  Structural Requirements for Potent Inhibition of <i>α</i>-Chymotrypsin
  作者：Kiyoko Iijima、Jun Katada、Emiko Yasuda、Isao Uno、Yoshio Hayashi

  DOI：10.1021/jm980562h

  日期：1999.1.1

  We introduce a new potent inhibitor, N-[2, 2-dimethyl-3-(N-(4-cyanobenzoyl)amino)nonanoyl]-L-phenylalanine ethyl ester (3), which preferentially inhibits serine proteases belonging to a chymotrypsin superfamily. This inhibitor, despite consisting of a stable ethyl ester structure, showed strong inhibitory activities toward bovine alpha-chymotrypsin, human cathepsin G, and porcine elastase by acting

  我们介绍了一种新的强效抑制剂，N- [2,2-二甲基-3-（N-（4-氰基苯甲酰基）氨基）壬酰基] -L-苯丙氨酸乙酯（3），它优先抑制属于胰凝乳蛋白酶超家族的丝氨酸蛋白酶。 。该抑制剂尽管由稳定的乙酯结构组成，但通过充当酰化剂，对牛α-胰凝乳蛋白酶，人组织蛋白酶G和猪弹性蛋白酶显示出强大的抑制活性。计算出的针对α-胰凝乳蛋白酶的失活速率常数（运动）和酶抑制剂解离常数（Ki）分别为0.0028 s-1和0.0045 microM（运动/ Ki = 630 000 M-1 s-1）。这些动力学参数表明该抑制剂是有史以来最强大的α-胰凝乳蛋白酶灭活剂之一。根据3的类似物的结构-活性关系（SAR）和结构-稳定性关系研究，在分子的三个部分（即4-氰基苯基），β-氨基酸残基处的β-取代基上进行了修饰以及酯结构，我们认为3的强抑制活性归因于以下结构特征：（1）强制特定酰基酶形成的乙酯，（2）β位置的正
• GPIIb/IIIa Integrin Antagonists with the New Conformational Restriction Unit, Trisubstituted β-Amino Acid Derivatives, and a Substituted Benzamidine Structure
  作者：Yoshio Hayashi、Jun Katada、Takeo Harada、Akira Tachiki、Kiyoko Iijima、Yoshimi Takiguchi、Michiko Muramatsu、Hiroshi Miyazaki、Tohru Asari、Takeo Okazaki、Yoshimi Sato、Emiko Yasuda、Mako Yano、Isao Uno、Iwao Ojima

  DOI：10.1021/jm980126v

  日期：1998.6.1

  Ethyl N- [3 -(2-fluoro-4-(thiazolidin-3-yl(imino)methyl)benzoyl)amino-2,2-dimethylpentanoyl]piperidine-4-acetate 40 (NSL-96184:) is a highly potent and orally active fibrinogen receptor antagonist, which is characterized by the presence of the trisubstituted beta-amino acid residue, 3 -ethyl-2,2-dimethyl-beta-alanine. This compound was developed on the basis of the SAR study of N-[3-(N-4-amidinobenzoyl)amino-2,2-dimethyl-3-phenylpropionyl]piperidine-4-acetic acid 1 (NSL-95301) with the derivatization focused on the central trisubstituted beta-amino acid unit as well as the basic amidinobenzoyl unit, and the esterification of the carboxyl group for prodrug composition, Compound 1, which was report;ed in our previous study, was discovered by the application of combinatorial chemistry. The molecular modeling study suggests that the trisubstituted beta-amino acid unit is responsible for fixing the molecule to its active conformation. Compound 40 showed an excellent profile in the in vitro and in vivo studies for its human platelet aggregation inhibitory activity and oral availability in guinea pigs. This oral availability largely depends on the modification of the amidino group with a cyclic secondary amine, i.e., thiazolidine in 40. In in vivo studies, the onset of the antiplatelet action of 40 is very fast after oral administration, whereas its duration of action is relatively short. These results suggest that 40 has an excellent therapeutic potential, especially for antithrombotic treatment in the acute phase. 3-Substituted-2,2-dimethyl-beta-amino acid residues would serve as new and useful linear templates to restrict the conformational flexibility of peptidomimetics.
• FIBRINOGEN RECEPTOR ANTAGONISTS HAVING SUBSTITUTED (b)-AMINO ACID RESIDUES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
  申请人：NIPPON STEEL CORPORATION

  公开号：EP0800516A1

  公开（公告）日：1997-10-15
• US5866592A
  申请人：——

  公开号：US5866592A

  公开（公告）日：1999-02-02
• [EN] FIBRINOGEN RECEPTOR ANTAGONISTS HAVING SUBSTITUTED beta -AMINO ACID RESIDUES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME<br/>[FR] ANTAGONISTES DES RECEPTEURS DU FIBRINOGENE PRESENTANT DES RESTES DE beta - AMINOACIDES SUBSTITUES ET PREPARATIONS PHARMACEUTIQUES LES COMPRENANT
  申请人：NIPPON STEEL CORPORATION

  公开号：WO1996020172A1

  公开（公告）日：1996-07-04

  (EN) Compounds of general formula (I) and pharmaceutically acceptable salts thereof.(FR) L'invention porte sur des composés de formule générale (I) et leurs sels pharmacocompatibles.