(S)-2-amino-N-phenethyl-3-phenylpropanamide | 35402-94-9

• 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: (S)-2-amino-N-phenethyl-3-phenylpropanamide
• 英文别名: (2S)-2-amino-3-phenyl-N-(2-phenylethyl)propanamide
• CAS: 35402-94-9
• 化学式: C₁₇H₂₀N₂O
• 分子量: 268.359
• InChiKey: RVOCIPPBVIEIKY-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-N-phenethyl-3-phenylpropanamide 在 盐酸 、 水 、 碳酸氢钠 作用下， 以 丙酮 为溶剂， 反应 1.05h， 生成 L-Phe-L-FDAA
  参考文献：
  名称：

  An Ugi-like Biosynthetic Pathway Encodes Bombesin Receptor Subtype-3 Agonists

  摘要：

  Isocyanide functional groups can be found in a variety of natural products. Rhabduscin is one such isocyanide-functionalized immunosuppressant produced in Xenorhabdus and Photorhabdus gammaproteobacterial pathogens, and deletion of its biosynthetic gene cluster inhibits virulence in an invertebrate animal infection model. Here, we characterized the first "opine-glycopeptide" class of natural products termed rhabdoplanins, and strikingly, these molecules are spontaneously produced from rhabduscin via an unprecedented multicomponent "Ugi-like" reaction sequence in nature. The rhabdoplanins also represent new lead G protein-coupled receptor (GPCR) agonists, stimulating the bombesin receptor subtype-3 (BB3) GPCR.

  DOI：

  10.1021/jacs.9b04183
• 作为产物：
  描述：

  苯丙酮酸 在 potassium permanganate 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 0.5h， 生成 (S)-2-amino-N-phenethyl-3-phenylpropanamide
  参考文献：
  名称：

  An Ugi-like Biosynthetic Pathway Encodes Bombesin Receptor Subtype-3 Agonists

  摘要：

  Isocyanide functional groups can be found in a variety of natural products. Rhabduscin is one such isocyanide-functionalized immunosuppressant produced in Xenorhabdus and Photorhabdus gammaproteobacterial pathogens, and deletion of its biosynthetic gene cluster inhibits virulence in an invertebrate animal infection model. Here, we characterized the first "opine-glycopeptide" class of natural products termed rhabdoplanins, and strikingly, these molecules are spontaneously produced from rhabduscin via an unprecedented multicomponent "Ugi-like" reaction sequence in nature. The rhabdoplanins also represent new lead G protein-coupled receptor (GPCR) agonists, stimulating the bombesin receptor subtype-3 (BB3) GPCR.

  DOI：

  10.1021/jacs.9b04183

文献信息

• Pd-Catalysed oxidative carbonylation of α-amino amides to hydantoins under mild conditions
  作者：Aleksandr Voronov、Vinayak Botla、Luca Montanari、Carla Carfagna、Raffaella Mancuso、Bartolo Gabriele、Giovanni Maestri、Elena Motti、Nicola Della Ca

  DOI：10.1039/d1cc04154a

  日期：——

  The first example of palladium-catalysed oxidative carbonylation of unprotected α-amino amides to hydantoins is described here. The selective synthesis of the target compounds was achieved under mild conditions (1 atm of CO), without ligands and bases. The catalytic system overrode the common reaction pathway that usually leads instead to the formation of symmetrical ureas.

  这里描述了钯催化氧化羰基化未保护的 α-氨基酰胺为乙内酰脲的第一个例子。目标化合物的选择性合成是在温和条件下（1 atm CO）实现的，无需配体和碱。催化系统超越了通常导致形成对称尿素的常见反应途径。
• [EN] HYDROXAMIC ACID DERIVATIVES FOR USE WITH THE TREATMENT OF DISEASES RELATED TO CONNECTIVE TISSUE DEGRADATION<br/>[FR] NOUVEAUX DERIVES D'ACIDE HYDROXAMIQUE UTILISES DANS LE TRAITEMENT DE MALADIES LIEES A UNE DEGRADATION DES TISSUS CONJONCTIFS
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：WO1997032846A1

  公开（公告）日：1997-09-12

  (EN) The present invention provides novel hydroxamic acid derivatives represented by the compound of formula (I), or pharmaceutical acceptable salts thereof, wherein the compounds of the present invention inhibit various enzymes from the matrix metalloproteinase family, including collagenase, stromelysin, and gelatinase, and hence are useful for the treatment of matrix metallo endoproteinase diseases such as osteoarthrits, rheumatoid arthritis, septic arthritis, osteopenias such as osteoporosis, tumor metastasis (invasion and growth), periodontitis, gingivitis, corneal ulceration, dermal ulceration, gastric ulceration, and other diseases related to connective tissue degradation.(FR) La présente invention concerne de nouveaux dérivés d'acide hydroxamique représentés par le composé de la formule générale (I) ou ses sels, acceptables sur le plan pharmaceutique. Les composés de l'invention inhibent différentes enzymes de la famille des métalloprotéinases matricielles, en particulier la collagénase, la stromélysine et la gélatinase. Ils sont donc utiles dans le traitement de maladies associées aux métalloendoprotéinases matricielles, telles que l'arthrose, la polyarthrite rhumatoïde, l'arthrite aiguë suppurée, les ostéopénies telles que l'ostéoporose, les métastases malignes (invasion et croissance) la périodontite, la gingivite, les ulcérations de la cornée, les ulcérations dermiques, les ulcérations gastriques et d'autres maladies liées à la dégradation du tissu conjonctif.

  本发明提供了由式（I）化合物表示的新型羟胺酸衍生物或其药学上可接受的盐，其中本发明的化合物抑制各种基质金属蛋白酶家族的酶，包括胶原酶、基质素和明胶酶，因此可用于治疗基质金属内蛋白酶疾病，如骨关节炎、类风湿性关节炎、化脓性关节炎、骨质疏松症如骨质疏松症、肿瘤转移（侵袭和生长）、牙周病、牙龈炎、角膜溃疡、皮肤溃疡、胃溃疡和其他与结缔组织降解相关的疾病。
• HYDROXAMIC ACID DERIVATIVES FOR USE WITH THE TREATMENT OF DISEASES RELATED TO CONNECTIVE TISSUE DEGRADATION
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP0898562B1

  公开（公告）日：2003-01-22
• Structure−Activity Relationships on Phenylalanine-Containing Inhibitors of Histone Deacetylase:  In Vitro Enzyme Inhibition, Induction of Differentiation, and Inhibition of Proliferation in Friend Leukemic Cells
  作者：Sybille Wittich、Hans Scherf、Changping Xie、Gerald Brosch、Peter Loidl、Clarissa Gerhäuser、Manfred Jung

  DOI：10.1021/jm0208119

  日期：2002.7.1

  Inhibitors of histone deacetylases (HDACs) are a new class of anticancer agents that affect gene regulation. We had previously reported the first simple synthetic HDAC inhibitors with in vitro activity at submicromolar concentrations. Here, we present structure-activity data on modifications of a phenylalanine-containing lead compound including amino acid amides as well as variations of the amino acid part. The compounds were tested for inhibition of maize HD-2, rat liver HDAC, and for the induction of terminal cell differentiation and inhibition of proliferation in Friend leukemic cells. In the amide series, in vitro inhibition was potentiated up to 15-fold, but the potential to induce cell differentiation decreased. Interestingly, an HDAC class selectivity was indicated among some of these amides. In the amino acid methyl ester series, a biphenylalanine derivative was identified as a good enzyme inhibitor, which blocks proliferation in the submicromolar range and is also a potent inducer of terminal cell differentiation.
• Chymotrypsin inhibitory conformation induced by amino acid side chain–side chain intramolecular CH/π interaction
  作者：Yasuyuki Shimohigashi、Iori Maeda、Takeru Nose、Koichi Ikesue、Hiroshi Sakamoto、Tomohisa Ogawa、Yuzuru Ide、Megumi Kawahara、Takashi Nezu、Yoshihiro Terada、Keiichi Kawano、Motonori Ohno

  DOI：10.1039/p19960002479

  日期：——

  Dipeptide amides H-D-Leu-Phe-NH-R have been found to assume a conformation induced by the CH/pi interaction and to inhibit chymotrypsin strongly. A series of benzyl amide derivatives H-D-Leu-Phe-NH-[CH2](n)-C6H5 (n = 0-4) have been assayed for chymotrypsin, They inhibit the enzyme in a competitive manner and the highest inhibition is achieved by the amide of n = 1 (K-1 3.6 x 10(-6) M), The activity enhancement is dependent upon the length of methylene chain, not upon the increase in molecular hydrophobicity, indicating the presence of an optimal distance between dipeptide backbone and C-terminal phenyl group for chymotrypsin inhibition, The C-terminal phenyl group has been found to interact with chymotrypsin stereospecifically, The R-isomer of H-D-Leu-Phe-NH-CH(CH3)-C6H5 is as active as the benzyl amide, while the S-isomer is about twenty-fold less active, When the fluorine atom is introduced at a para-position of the C-terminal phenyl group, the resulting dipeptide H-D-Leu-Phe-NH-CH2-C6H4F-p exhibits about six-times increased inhibitory activity (K-1 = 6.1 x 10(-7) M; this dipeptide is one of the most potent chymotrypsin inhibitors to date), H-1 NMR conformational analyses of these dipeptide amide derivatives show the CH/pi: interaction between D-Leu-isobutyl and Phe-phenyl as a key structural element for chymotrypsin inhibition, These structural examinations strongly suggest that in the inhibitory conformation the C-terminal phenyl group fits the chymotrypsin S-1 site, while the hydrophobic core constructed by D-Leu-Phe CH/pi interaction fits the chymotrypsin S-2 or S-1' site.