methyl (2S,5R)-(+)-5-phenylpyrrolidine-2-carboxylate | 153242-44-5

• 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
• 英文名称: methyl (2S,5R)-(+)-5-phenylpyrrolidine-2-carboxylate
• 英文别名: (2S,5R)-methyl 5-phenylpyrrolidine-2-carboxylate；methyl (2S,5R)-5-phenylpyrrolidine-2-carboxylate
• CAS: 153242-44-5
• 化学式: C₁₂H₁₅NO₂
• 分子量: 205.257
• InChiKey: PLTYXWQEMLQCPO-MNOVXSKESA-N

物化性质

• 沸点：
  303.2±42.0 °C(Predicted)
• 密度：
  1.100±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (2S,5R)-(+)-5-phenylpyrrolidine-2-carboxylate 在 palladium on activated charcoal 盐酸 、 三聚氯氰 、 氢气 、 1-羟基苯并三唑 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 为溶剂， 反应 4.0h， 生成 (2S,5R)-1-[2-((S)-2-Acetylsulfanyl-3-phenyl-propionylamino)-acetyl]-5-phenyl-pyrrolidine-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Design of Orally Active Dual Inhibitors of Neutral Endopeptidase and Angiotensin-Converting Enzyme with Long Duration of Action

  摘要：

  Mercaptoacyl dipeptides, containing a glycine Linked to a C-terminal 5-phenylproline, have been synthesized in order to obtain new highly efficient dual inhibitors of the two zinc metallopeptidases, neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), which are involved in the control of blood pressure and fluid homeostasis. These compounds have been designed (i) to fit optimally the ACE pharmacophore previously described (Fournie-Zaluski, M. C.; et al. J. Med. Chem. 1994, 37, 1070-1083), through interaction with the S-1, S-1', and S-2' subsites of this enzyme, (ii) and to interact with the S-1' and S-2' subsites of NEP with the 5-phenylproline moiety outside the catalytic domain (Coric, P.; et al. J. Med. Chem. 1996, 39, 1210-1219). Replacement of Gly by Ala in these mercaptoacyl dipeptides induced an about 100-fold decreasein ACE inhibition. This shows that, in agreement with molecular modeling studies, a steric constraint as weak as a methyl group hinders optimal ACE active site recognition, Among these compounds, the dual inhibitor 26 (RB 106) (K-i, ACE =: 0.35 nM; NEP = 1.6 nM) showed excellent pharmacokinetic properties with an almost complete in vivo inhibition of NEP and ACE for more than 4 h after oral administration in mice of a low dose (2.6 x 10(-5) mol/kg) of the inhibitor. Moreover, RE 106 remained active 12 h after oral administration In spontaneous hypertensive rats, a chronic treatment of orally administered RB 106 (25 mg/kg/day) induced a prolonged hypotensive effect (-28 mmHg) still significant 2 days after the end of the treatment. In DOCA salt rats, a hypotensive response and a significant natriuresis were observed after iv administration RE 106, which is one of the most potent dual inhibitors described to date, could have interesting clinical applications in long term treatment of congestive heart failure and myocardial ischemia.

  DOI：

  10.1021/jm950783c
• 作为产物：
  描述：

  L-焦谷氨酸甲酯 在 4-二甲氨基吡啶 、 氢气 、 碘 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， -30.0~20.0 ℃ 、101.33 kPa 条件下， 反应 80.0h， 生成 methyl (2S,5R)-(+)-5-phenylpyrrolidine-2-carboxylate
  参考文献：
  名称：

  分子内烷基化方法合成双环和三环手性胍盐

  摘要：

  描述了导致三种新型手性胍支架的合成研究。感兴趣的结构包括在胍核心周围具有各种取代模式的双环胍衍生物，以及高度刚性的三环支架。通过应用汞 (II) 促进的 N-Boc 取代硫脲的鸟苷酸化和 Ishikawa 的脱硫环化来获得具有挑战性的目标。除了我们的合成逻辑之外，还介绍了三环胍盐的可扩展合成。

  DOI：

  10.1002/ejoc.201601154

文献信息

• [EN] COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING INFLAMMATORY DISEASES<br/>[FR] COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET MÉTHODES À UTILISER DANS LE TRAITEMENT DE MALADIES INFLAMMATOIRES
  申请人：EUROSCREEN SA

  公开号：WO2015078949A1

  公开（公告）日：2015-06-04

  The present invention is directed to compounds of formula (I), useful in treating and/or preventing inflammatory diseases.

  本发明涉及一种化合物，其化学式为(I)，用于治疗和/或预防炎症性疾病。
• Pyrrolidine and thiazolidine derivatives, their preparation and
  申请人：Rhone-Poulenc Rorer S.A.

  公开号：US05610144A1

  公开（公告）日：1997-03-11

  This invention relates to compositions of formula: ##STR1## and their salts, their preparation and the medicaments containing them.

  这项发明涉及以下结构的化合物：##STR1##及其盐，它们的制备以及含有它们的药物。
• Cold Menthol Receptor Antagonists
  申请人：Colburn Raymond W.

  公开号：US20100048589A1

  公开（公告）日：2010-02-25

  Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula I as follows: wherein A, B, L, Q, R 1 , R 2 , and R 3 are defined herein.

  揭示了用于治疗各种疾病、综合症、症状和障碍的化合物、组合物和方法，包括疼痛。这些化合物由以下的化学式 I 表示：其中 A、B、L、Q、R1、R2 和 R3 在此处定义。
• Synthesis of cis-2,5-disubstituted pyrrolidines via diastereoselective reduction of N-acyl iminium ions
  作者：Alexander C Rudolph、Rainer Machauer、Stephen F Martin

  DOI：10.1016/j.tetlet.2004.04.122

  日期：2004.6

  A new procedure for forming cis-2,5-disubstituted pyrrolidines having unsaturated side chains has been developed that features the diastereoselective reduction of N-acyl iminium ions, which were formed in situ by acid-catalyzed cyclizations of unsaturated γ-keto carbamates, with triphenylsilane. The sequence was applied to a very concise synthesis of 16, a subunit in the nonpeptide cholecystokinin

  已经开发出形成具有不饱和侧链的顺式-2,5-二取代的吡咯烷的新方法，其特征在于通过酸催化不饱和γ-酮氨基甲酸酯的环化反应原位形成的N-酰基亚氨基离子的非对映选择性还原。三苯基硅烷。将该序列应用于非常简洁的16合成，该合成是非肽胆囊收缩素拮抗剂（+）-RP-66803中的一个亚基。
• Binap-silver salts as chiral catalysts for the enantioselective 1,3-dipolar cycloaddition of azomethine ylides and alkenes
  作者：Juan Mancebo-Aracil、María Martín-Rodríguez、Carmen Nájera、José M. Sansano、Paulo R.R. Costa、Evanoel Crizanto de Lima、Ayres G. Dias

  DOI：10.1016/j.tetasy.2012.10.015

  日期：2012.12

  Binap-AgSbF6 catalyzed 1,3-dipolar cycloadditions between azomethine ylides and electrophilic alkenes are described and compared with analogous transformations mediated by other Binap-silver(I) salt complexes. Maleimides and 1,2-bis(phenylsulfonyl)ethylene are suitable dipolarophiles for obtaining very good enantioselectivities, even better values are generated by a multicomponent version. There are

  描述了Binap-AgSbF 6催化的甲亚胺烷基化物和亲电子烯烃之间的1,3-偶极环加成反应，并将其与其他Binap-银（I）盐配合物介导的类似转化进行了比较。马来酰亚胺和1，2-双（苯磺酰基）乙烯是获得非常好的对映选择性的合适的双亲亲油性，甚至通过多组分形式产生更好的对映选择性。二磺酰化的环加合物在顺式2,5-二取代的吡咯烷，天然产物的前体或抗病毒化合物的合成中有价值的中间体的总合成中有一些非常有趣的应用。