2-苄基-5-氰基-4-氧代戊酸 | 126121-83-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 中文名称: 2-苄基-5-氰基-4-氧代戊酸
• 英文名称: (R)-2-benzyl-5-cyano-4-oxopentanoic acid
• 英文别名: 2-Benzyl-5-cyano-4-oxopentanoic acid；(2R)-2-benzyl-5-cyano-4-oxopentanoic acid
• CAS: 126121-83-3
• 化学式: C₁₃H₁₃NO₃
• 分子量: 231.251
• InChiKey: AQDFTKPHMZIIEF-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  78.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-苄基-5-氰基-4-氧代戊酸 在 sodium hydroxide 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 N-<(R)-2-benzyl-5-cyano-4-oxopentanoyl>-L-phenylalanine
  参考文献：
  名称：

  The first mechanism-based inactivators for angiotensin-converting enzyme

  摘要：

  The first example of mechanism-based inactivation of angiotensin-converting enzyme (ACE) is described for N-[N-(cyanoacetyl)-L-phenylalanyl]-L-phenylalanine (compound 1). It is proposed that an ACE-mediated deprotonation of 1 unmasks a ketenimine intermediate, which traps an active-site nucleophile, and hence irreversibly modifies the enzyme. In competition with the inactivation reaction, ACE also hydrolyzes 1 with a partition ratio of 8300 (i.e., k(cat)/k(inact)). Since the corresponding keto analogue, N-[(R)-2-benzyl-5-cyano-4-oxopentanoyl]-L-phenylalanine (compound 4), does not inactivate the enzyme, it is suggested that the NH in compound 1 is critical for the proper active-site anchoring of the inhibitor for the inactivation process to take place.

  DOI：

  10.1021/jm00100a024
• 作为产物：
  描述：

  (R)-(+)-二甲基苄基琥珀酸 、 乙腈 在 正丁基锂 作用下， 生成 2-苄基-5-氰基-4-氧代戊酸
  参考文献：
  名称：

  The first mechanism-based inactivators for angiotensin-converting enzyme

  摘要：

  The first example of mechanism-based inactivation of angiotensin-converting enzyme (ACE) is described for N-[N-(cyanoacetyl)-L-phenylalanyl]-L-phenylalanine (compound 1). It is proposed that an ACE-mediated deprotonation of 1 unmasks a ketenimine intermediate, which traps an active-site nucleophile, and hence irreversibly modifies the enzyme. In competition with the inactivation reaction, ACE also hydrolyzes 1 with a partition ratio of 8300 (i.e., k(cat)/k(inact)). Since the corresponding keto analogue, N-[(R)-2-benzyl-5-cyano-4-oxopentanoyl]-L-phenylalanine (compound 4), does not inactivate the enzyme, it is suggested that the NH in compound 1 is critical for the proper active-site anchoring of the inhibitor for the inactivation process to take place.

  DOI：

  10.1021/jm00100a024

文献信息

• [EN] DIPEPTIDE-ANALOG-BASED METALLOENDOPEPTIDASE INHIBITORS AND METHODS OF USING SAME
  申请人：THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ASSOCIATES, INC.

  公开号：WO1991005763A1

  公开（公告）日：1991-05-02

  (EN) Inhibitors of the Zn+2-metalloendopeptidases, enkephalinase, angiotensin-converting enzyme, and collagenase are provided. The enkephalinase inhibitors of the invention are useful as analgesics or antihypertensives. The angiotensin-converting enzyme inhibitors of the invention are useful as antihypertensives. The collagenase inhibitors of the invention are useful in treating diseases, such as corneal ulceration, periodontal disease, and arthritis, which involve undesirable activity of bacterial or mammalian collagenases. The inhibitors of the invention are peptide or peptide-ester derivatives of the dipeptide analogs of the formula X1-(CR3R4)z-(CR5R6)x-CHR9-CO2H wherein X1- is a functional group, such as (N=C) (CH2) (C=0)-, from which a Zn+2 metalloendopeptidase, at its active site, is capable of abstracting a proton to yield and activated functional group capable of forming a stable, covalent bond with a residue in the active site; z is 0 or 1, wherein, when z is 0, the group -(CR3R4)z-(CR5R6)x- is not in the compound and the group X1-is bonded directly to the group -(CHR9)-; x is 0 if z is 0 or is 0 or 1 if z is 1, wherein, when x is 0 and z is 1, the group -(CR5R6)x- is not in the compound and the group -(CR3R4)- is bonded directly to the group -(CHR9)-; R2, R3, R4, R5, and R6 are independently hydrogen or alkyl of 1 to 3 carbon atoms; and R9 is benzyl, alkyl of 1 to 5 carbon atoms, or hydrogen. Among the dipeptide analogs derivatized with peptides or peptide esters in accordance with the invention is 2-benzyl-5-cyano-4-oxopentanoic acid, which the invention provides substantially free of its 3- benzyl regioisomer.(FR) Inhibiteurs de Zn+2-métalloendopeptidases d'enképhalinase, d'enzyme de conversion d'angiotensine, et de collagénase. Les inhibiteurs d'enképhalinase de l'invention sont utiles comme analgésiques ou anti-hypertenseurs. Les inhibiteurs d'enzyme de conversion d'angiotensine de l'invention sont utiles en tant qu'anti-hypertenseurs. Les inhibiteurs de collagénase de l'invention sont utiles dans le traitement de maladies, telles que l'ulcération de la cornée, la paradontolyse, et l'arthrite, lesquelles impliquent une activité indésirable de collagénases bactériennes ou mammifères. Les inhibiteurs de l'invention sont des dérivés peptidiques ou d'esters peptidiques d'analogues dipeptidiques de la formule X1-(CR3R4)z-(CR5R6)x-CHR9CO2H, dans laquelle X1- représente un groupe fonctionnel, tel que (N|||C) (CH2) (C=O)-, duquel une Zn+2 métalloendopeptidase, au niveau de son site actif, est capable de soustraire un proton afin de produire un groupe fonctionnel activé capable de former une liaison covalente stable avec un résidu se trouvant dans le site actif; z représente 0 ou 1, dans laquelle, lorsque z représente 0, le groupe -(CR3R4)z- (CR5R6)x- ne représente pas le composé et le groupe X1- est lié directement au groupe -(CHR9)-; x représente 0 si z représente 0, ou il représente 0 ou 1 si z représente 1, dans laquelle, lorsque x représente 0 et z représente 1, le groupe -(CR5R6)x- ne représente pas le composé et le groupe -(CR3R4)- est lié directement au groupe -(CHR9)-; R3, R4, R5 et R6 représentent indépendamment hydrogène ou alkyle contenant 1 à 3 atomes de carbone; et R9 représente benzyl, alkyl contenant 1 à 5 atomes de carbone, ou hydrogène. Parmi les analogues dipeptidique transformés par dérivation à l'aide de peptides ou d'esters peptidiques selon l'invention, se trouve l'acide 2-benzyl-5-cyano-4-oxopentanoïque, que l'invention produit exempt de son régioisomère de 3-benzyl.
• The first mechanism-based inactivators for angiotensin-converting enzyme
  作者：Soumitra S. Ghosh、Odile Said-Nejad、Juliatiek Roestamadji、Shahriar Mobashery

  DOI：10.1021/jm00100a024

  日期：1992.10

  The first example of mechanism-based inactivation of angiotensin-converting enzyme (ACE) is described for N-[N-(cyanoacetyl)-L-phenylalanyl]-L-phenylalanine (compound 1). It is proposed that an ACE-mediated deprotonation of 1 unmasks a ketenimine intermediate, which traps an active-site nucleophile, and hence irreversibly modifies the enzyme. In competition with the inactivation reaction, ACE also hydrolyzes 1 with a partition ratio of 8300 (i.e., k(cat)/k(inact)). Since the corresponding keto analogue, N-[(R)-2-benzyl-5-cyano-4-oxopentanoyl]-L-phenylalanine (compound 4), does not inactivate the enzyme, it is suggested that the NH in compound 1 is critical for the proper active-site anchoring of the inhibitor for the inactivation process to take place.