(4S)-4-苄基-3-(5-苯基戊酰基)-1,3-恶唑烷-2-酮 | 161725-13-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: (4S)-4-苄基-3-(5-苯基戊酰基)-1,3-恶唑烷-2-酮
• 英文名称: (4S)-4-benzyl-3-(5-phenylpentanoyl)-1,3-oxazolidin-2-one
• 英文别名: (S)-4-benzyl-3-(5-phenylpentanoyl)oxazolidin-2-one；3-phenylpentanoyl-4(S)-benzyl-2-oxazolidinone
• CAS: 161725-13-9
• 化学式: C₂₁H₂₃NO₃
• 分子量: 337.419
• InChiKey: KEGIFRQLJWATJK-IBGZPJMESA-N

物化性质

• 沸点：
  528.9±29.0 °C(Predicted)
• 密度：
  1.175±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4S)-4-苄基-3-(5-苯基戊酰基)-1,3-恶唑烷-2-酮 在 lithium hydroxide 、 双氧水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium diisopropyl amide 、 sodium nitrite 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 tert-butyl (3R)-3-[[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]-6-phenylhexanoate
  参考文献：
  名称：

  Inhibition of Membrane-Type 1 Matrix Metalloproteinase by Hydroxamate Inhibitors:  An Examination of the Subsite Pocket

  摘要：

  The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been reported to mediate the activation of pro-gelatinase A (proMMP-2), which is associated with tumor proliferation and metastasis. MT1-MMP can also digest extracellular matrix (ECM) such as interstitial collagens, gelatin, and proteoglycan and thus may play an important role in pathophysiological digestion of ECM. We studied the inhibitory effect of various hydroxamate MMP inhibitors, including known inhibitors such as BB-94, BB-2516, GM6001, and Ro31-9790, on a deletion mutant of MT1-MMP lacking the transmembrane domain (Delta MT1) to further characterize the enzyme and develop a selective inhibitor for MT1-MMP. The evaluation of the inhibitory activities of various hydroxamates reveals general structural profiles affecting selectivities toward MMPs. In particular, a longer side chain at the P1' position is preferable for the binding to MMP-2, -3, and -9 and MT1-MMP. For the P2' position, an a-branched alkyl group is critical for the binding toward Delta MT1, while the introduction of a bulky group at the a-position of hydroxamic acid seems to diminish the activity against Delta MT1. Summation of the data on the sensitivity of Delta MT1 to various hydroxamate inhibitors indicates that (1) the volume of the S1' subsite of Delta MT1 is similar to that of MMP-2, -3, and -9, which is bigger than that of MMP-1, and (2) the S1 and S2' subsites are narrower than those in other MMPs. On the basis of these results, the hydroxamates with a P1' phenylpropyl and P2' alpha-branched alkyl group were synthesized and evaluated for inhibitory activity. These inhibitors (1h,i) showed strong activity against Delta MT1 over MMP-1, but no selectivity between Delta MT1 and MMP-9. These results are explained using molecular modeling studies conducted on MT1-MMP.

  DOI：

  10.1021/jm970404a
• 作为产物：
  描述：

  5-苯基戊酸 在 正丁基锂 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.0h， 生成 (4S)-4-苄基-3-(5-苯基戊酰基)-1,3-恶唑烷-2-酮
  参考文献：
  名称：

  [EN] DIFLUOROLACTAM COMPOSITIONS FOR EP4-MEDIATED OSTEO RELATED DISEASES AND CONDITIONS
  [FR] COMPOSITIONS DE DIFLUOROLACTAME DESTINÉES À DES MALADIES ET DES AFFECTIONS OSSEUSES MÉDIÉES PAR EP4

  摘要：

  披露的是通过给予公式(I)化合物的组合物和方法来治疗骨质疏松症、骨折、骨丢失以及增加骨密度，其中组合物包含公式(I)的化合物和药用可接受的载体，其中L1、L2、L4、R1、R4、R5、R6和s按说明书定义。

  公开号：

  WO2014015246A1

文献信息

• [EN] LACTAM COMPOUNDS AS EP4 RECEPTOR-SELECTIVE AGONISTS FOR USE IN THE TREATMENT OF EP4-MEDIATED DISEASES AND CONDITIONS<br/>[FR] COMPOSÉS LACTAMES EN TANT QU'AGONISTES SÉLECTIFS DU RÉCEPTEUR EP4 POUR L'UTILISATION DANS LE TRAITEMENT DE MALADIES ET D'ÉTATS À MÉDIATION PAR EP4
  申请人：CAYMAN CHEMICAL CO INC

  公开号：WO2014144610A1

  公开（公告）日：2014-09-18

  Disclosed herein are compounds of formula (I) wherein L1, L2, L3, R1, R4, R5, and R6 are as defined in the specification. Compounds of formula (I) are EP4 agonists useful in the treatment of glaucoma, osteoporosis, bone fracture, periodontal bone loss, orthopedic implant, alopecia, neuropathic pain, and related disorders. Pharmaceutical compositions and methods of treating conditions or disorders are also described.

  披露了公式(I)的化合物，其中L1、L2、L3、R1、R4、R5和R6如说明书定义。公式(I)的化合物是EP4激动剂，可用于治疗青光眼、骨质疏松症、骨折、牙周骨丢失、骨科植入物、脱发、神经性疼痛及相关疾病。还描述了药物组合物和治疗条件或疾病的方法。
• Synthesis and SAR of succinamide peptidomimetic inhibitors of cathepsin S
  作者：Arnab K. Chatterjee、Hong Liu、David C. Tully、Jianhua Guo、Robert Epple、Ross Russo、Jennifer Williams、Michael Roberts、Tove Tuntland、Jonathan Chang、Perry Gordon、Thomas Hollenbeck、Christine Tumanut、Jun Li、Jennifer L. Harris

  DOI：10.1016/j.bmcl.2007.02.049

  日期：2007.5

  Peptidic, non-covalent inhibitors of lysosomal cysteine protease cathepsin S (1 and 2) were investigated due to low oral bioavailability, leading to an improved series of peptidomimetic inhibitors. Utilizing phenyl succinamides as the P2 residue increased the oral exposure of this lead series of compounds, while retaining selective inhibition of the cathepsin S isoform. Concurrent investigation of

  由于口服生物利用度低，研究了溶酶体半胱氨酸蛋白酶组织蛋白酶S（1和2）的肽类非共价抑制剂，从而产生了一系列拟肽抑制剂。使用苯基琥珀酰亚胺作为P2残基可增加该先导系列化合物的口腔暴露，同时保留对组织蛋白酶S亚型的选择性抑制作用。对P1和P2亚位点的同时研究导致发现了几种有效的和选择性的组织蛋白酶S抑制剂，这些酶由于消除了饱和脂肪族P2残基而具有良好的药代动力学特性。
• Fas LIGAND SOLUBILIZATION INHIBITOR
  申请人：KANEBO LTD.

  公开号：EP0848957A1

  公开（公告）日：1998-06-24

  A Fas ligand solubilization inhibitor which comprises, as the active ingredient, a compound of the generic formula (I) having a matrix metalloproteinase inhibitory activity or its pharmaceutically acceptable salt. The drug is useful in the prevention or treatment of diseases caused by solubilized Fas ligand, such as hepatitis, GVHD, AIDS, autoimmune diseases, etc.

  一种Fas配体溶解抑制剂，其活性成分为具有基本结构式（I）的化合物，具有基质金属蛋白酶抑制活性或其药用盐。该药物可用于预防或治疗由溶解的Fas配体引起的疾病，如肝炎、移植物抗宿主病、艾滋病、自身免疫疾病等。
• Asymmetric reactions of chiral imide enolates with α-keto esters
  作者：Irina C. Jacobson、G.Prabhakar Reddy

  DOI：10.1016/0040-4039(96)01843-6

  日期：1996.11

  A method for the synthesis of a variety of 2-hydroxy-2,3-trisubstituted succinates (I) is presented. The synthesis is achieved by the asymmetric reactions of lithium, boron or titanium enolates of Evans' chiral imides with α-keto esters.

  提出了一种合成各种2-羟基-2，3-三取代的琥珀酸酯（I）的方法。合成是通过Evans手性酰亚胺的锂，硼或钛的烯醇化物与α-酮酸酯的不对称反应实现的。
• Compounds having lysophosphatidic acid receptor antagonism and uses thereof
  申请人：Tanaka Motoyuki

  公开号：US20070149595A1

  公开（公告）日：2007-06-28

  The present invention relates to a compound represented by formula (I): (wherein the symbols in formula were described in the description), a salt thereof, a solvate thereof or a prodrug thereof. Since the compound of the present invention binds to and is antagonistic to an LPA receptor (particularly, EDG-2), it is useful for prevention and/or treatment of urinary system disease (prostatic hypertrophy or neurogenic bladder dysfunction disease, spinal cord neoplasm, nucleous hernia, spinal canal stenosis, diseases caused by diabetes, occlusion disease of lower urinary tract, inflammatory disease of lower urinary tract, and polyuria), carcinoma-associated disease, proliferative disease, inflammation system disease, immune system disease, disease by secretory dysfunction, brain-related disease and/or chronic disease.

  本发明涉及一种由式(I)表示的化合物：（其中式中的符号在说明中被描述），其盐，溶剂化物或前药。由于本发明的化合物与LPA受体（特别是EDG-2）结合并具有拮抗作用，因此它对预防和/或治疗泌尿系统疾病（前列腺增生或神经源性膀胱功能障碍疾病，脊髓肿瘤，核突出，脊柱管狭窄，由糖尿病引起的疾病，下尿路梗阻疾病，下尿路炎症性疾病和多尿症），癌症相关疾病，增殖性疾病，炎症系统疾病，免疫系统疾病，分泌功能障碍疾病，与大脑相关的疾病和/或慢性疾病具有用处。