N-Boc-beta-n-butyl-alpha,alpha-dimethyl-beta-alanine | 180181-88-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-Boc-beta-n-butyl-alpha,alpha-dimethyl-beta-alanine
• 英文别名: 2,2-dimethyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]heptanoic acid
• CAS: 180181-88-8
• 化学式: C₁₄H₂₇NO₄
• 分子量: 273.373
• InChiKey: INEGTXIMOPLDGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-Boc-beta-n-butyl-alpha,alpha-dimethyl-beta-alanine 在 苯甲醚 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 生成
  参考文献：
  名称：

  GPIIb/IIIa Integrin Antagonists with the New Conformational Restriction Unit, Trisubstituted β-Amino Acid Derivatives, and a Substituted Benzamidine Structure

  摘要：

  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.

  DOI：

  10.1021/jm980126v
• 作为产物：
  描述：

  N-trimethylsilylpentan-1-imine 在 盐酸 、 sodium carbonate 、 lithium diisopropyl amide 作用下， 以 1,4-二氧六环 为溶剂， 反应 44.0h， 生成 N-Boc-beta-n-butyl-alpha,alpha-dimethyl-beta-alanine
  参考文献：
  名称：

  GPIIb/IIIa Integrin Antagonists with the New Conformational Restriction Unit, Trisubstituted β-Amino Acid Derivatives, and a Substituted Benzamidine Structure

  摘要：

  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.

  DOI：

  10.1021/jm980126v

文献信息

• Fibrinogen receptor antagonist and pharmaceutical compositions
  申请人：Nippon Steel Corporation

  公开号：US05866592A1

  公开（公告）日：1999-02-02

  Compounds of the following general formula (I) and pharmaceutically acceptable salts thereof.

  以下一般式(I)的化合物及其药学上可接受的盐。
• FIBRINOGEN RECEPTOR ANTAGONISTS HAVING SUBSTITUTED (b)-AMINO ACID RESIDUES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
  申请人：Nippon Steel Corporation

  公开号：EP0800516B1

  公开（公告）日：2001-09-19
• 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.
• 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.