(R)-2-bromo-4-phenylbutyric acid | 121842-76-0

• 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: (R)-2-bromo-4-phenylbutyric acid
• 英文别名: (R)-2-bromo-4-phenylbutanoic acid；(R)-2-Bromo-4-phenylbutanoicacid；(2R)-2-bromo-4-phenylbutanoic acid
• CAS: 121842-76-0
• 化学式: C₁₀H₁₁BrO₂
• 分子量: 243.1
• InChiKey: DJQJKQPODCNTSE-SECBINFHSA-N

物化性质

• 沸点：
  315.7±22.0 °C(Predicted)
• 密度：
  1.487±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-2-bromo-4-phenylbutyric acid 在 氯化亚砜 、 碳酸氢铵 、 三氟乙酸 作用下， 以 硝基甲烷 、 水 为溶剂， 反应 123.0h， 生成 依那普利
  参考文献：
  名称：

  A practical and diastereoselective synthesis of angiotensin converting enzyme inhibitors.

  摘要：

  描述了一系列有效的血管紧张素转化酶（ACE）抑制剂的立体选择性合成。通过微生物氢氨酰化酶的不对称水解法，制备了光学活性中间体N-carbamyl (R)-2-amino-4-phenylbutyric acid (2)，该中间体可进一步转化为(R)-2-卤代或(R)-2-羟基-4-苯基丁酸。卤代酯通过SN2反应与L-氨基酸衍生物反应，生成N-取代氨基酸，这些化合物通过去保护反应可以很容易转化为ACE抑制剂或中间体。

  DOI：

  10.1248/cpb.37.280
• 作为产物：
  描述：

  N-氨基甲酰基(R)-2-氨基-4-苯基丁酸 在 硫酸 、 potassium bromide 、 sodium nitrite 作用下， 生成 (R)-2-bromo-4-phenylbutyric acid
  参考文献：
  名称：

  A practical and diastereoselective synthesis of angiotensin converting enzyme inhibitors.

  摘要：

  描述了一系列有效的血管紧张素转化酶（ACE）抑制剂的立体选择性合成。通过微生物氢氨酰化酶的不对称水解法，制备了光学活性中间体N-carbamyl (R)-2-amino-4-phenylbutyric acid (2)，该中间体可进一步转化为(R)-2-卤代或(R)-2-羟基-4-苯基丁酸。卤代酯通过SN2反应与L-氨基酸衍生物反应，生成N-取代氨基酸，这些化合物通过去保护反应可以很容易转化为ACE抑制剂或中间体。

  DOI：

  10.1248/cpb.37.280

文献信息

• Acylmercaptoalkanoyldipeptides, methods of preparation and their therapeutic use
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP0524553A1

  公开（公告）日：1993-01-27

  This invention is directed to a compound of the formula that inhibits simultaneously neutral endopeptidase and peptidyldipeptidase A and is useful in treating hypertension. The invention is also directed to the preparation of the compound, pharmaceutical compositions containing it, and methods for its pharmaceutical use.

  这项发明涉及一种化合物，该化合物能同时抑制中性内肽酶和肽二肽酶A，并可用于治疗高血压。该发明还涉及该化合物的制备，含有该化合物的药物组合物，以及该药物的使用方法。
• ACE-2 modulating compounds and methods of use thereof
  申请人：——

  公开号：US20040082496A1

  公开（公告）日：2004-04-29

  ACE-2 modulating compounds for the treatment of body weight disorders are disclosed. Methods of using the compounds and pharmaceutical compositions containing the compounds are also claimed.

  抗ACE-2调节化合物用于治疗体重失调的方法已被披露。还声称了使用这些化合物的方法和含有这些化合物的药物组合物。
• Optimal Recognition of Neutral Endopeptidase and Angiotensin-Converting Enzyme Active Sites by Mercaptoacyldipeptides as a Means To Design Potent Dual Inhibitors
  作者：Pascale Coric、Serge Turcaud、Hervé Meudal、Bernard Pierre Roques、Marie-Claude Fournie-Zaluski

  DOI：10.1021/jm950590p

  日期：1996.3.15

  An interesting approach for the treatment of congestive heart failure and chronic hypertension could be to avoid the formation of angiotensin II by inhibiting angiotensin converting enzyme (ACE) and to protect atrial natriuretic factor by blocking neutral endopeptidase 24.11 (NEP). This is support-ed by recent results obtained with potent dual inhibitors of the two zinc metallopeptidases, such as RE 105, HSCH2CH(CH3)PhCONHCH(CH3)COOH (Fournie-Zaluski et rrl. Proc, Natl. Acad. Sci. U.S.A, 1994, 91, 4072-4076), which reduces blood pressure in experimental models of hypertension, independently of the stilt and renin angiotensin system status, In order to develop new dual inhibitors with improved affinities, long duration of action, and/or better bioavailabilities, various series of mercaptoacyldipeptides corresponding to the general formula HSCH(R(1))CONHCH(R(1)')CON(R)CH(R(2)')COOH have been si synthesized. The introduction of well-selected beta-branched chains in positions R(1) and R(1)', associated with a tyrosine or a cyclic amino acid in the C-terminal position, led to potent dual inhibitors of NEP and ACE; such as 21 [N-[(2S)-2-mercapto-3-methylbutanoyl]-Ile-Try] and 22 [N-[(2S)-2-mercapto-3-phenylpropanoyl]Ala-Pro] which have IC50 values in the nanomolar range for NEP and subnanomolar range for ACE, These compounds could have different modes of binding to the two peptidases. In NEP, the dual inhibitors seem to interact only with the S-1' and S-2' subsites, whereas additional interactions with the Si binding subsite of ACE probably account fbr their subnanomolar inhibitory potencies for this enzyme. The localization of the Pro residue of 22 outside the NEP active site is supported by biochemical data using (Arg(102),Glu)NEP and molecular modeling studies with thermolysin used as model of WE:P. One hour after oral administration in mice of a single dose (2.7 x 10(-5) mol/kg, 21 inhibited 80% and 36% of kidney NEP and lung ACE, respectively, while 22 inhibited 40% of kidney NEP and 56% of lung ACE.
• New Thiol Inhibitors of Neutral Endopeptidase EC 3.4.24.11: Synthesis and Enzyme Active-Site Recognition
  作者：Isabel Gomez-Monterrey、Ann Beaumont、Patrick Nemecek、Bernard P. Roques、Marie-Claude Fournie-Zaluski

  DOI：10.1021/jm00038a016

  日期：1994.6

  Selective, as well as mixed, inhibitors of the two zinc metallopeptidases, neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE), are of major clinical interest in the treatment of hypertension and cardiac failure. New thiol inhibitors, corresponding to the general formula HS-CH(R(1))-CH2-CH(R(2))-CONH-CH(R(3))-COOH, were designed in order to explore the putative S-1 subsite of the active site of NEP. The inhibitors were also tested on ACE and the most representative on thermolysin (TLN) for comparison. The relatively low inhibitory potencies exhibited by these compounds (IC(50)s in the 10(-7) M range for NEP and in the 10(-6) M range for ACE) as compared to that of thiorphan (IC(50)s 2 10 X 10(-9) M on NEP and 1.40 x 10(-7) M on ACE) clearly indicate the absence of the expected energetically favorable interactions with the active site of both peptidases. A 100-fold loss of potency for these inhibitors was also observed for thermolysin as compared to thiorphan. Using the mutated Glu(102)-NEP, it was possible to demonstrate that the inhibitors do not fit the S-1 subsite of NEP but interact with the S-1' and S-2' subsites through binding of their R(1) and R(2) residues and that the C-terminal amino acid is located outside the active site. These results seem to indicate that these thiol inhibitors are not well. adapted for optimal recognition of the S-1 subsite of NEP, and probably ACE, and that other zinc-chelating moieties such as carboxylate or phosphonate groups may be preferred for this purpose.
• WASAKI, GENJI;KIMURA, RIEKO;NUMAO, NAGANORI;KONDO, KIYOSI, CHEM. AND PHARM. BULL., 37,(1989) N, C. 280-283
  作者：WASAKI, GENJI、KIMURA, RIEKO、NUMAO, NAGANORI、KONDO, KIYOSI

  DOI：——

  日期：——