N-(3,5-二氯苯磺酰基)-l-脯氨酸 | 217326-48-2

• 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
• 中文名称: N-(3,5-二氯苯磺酰基)-l-脯氨酸
• 英文名称: N-(3,5-dichlorobenzenesulfonyl)-2-(S)-proline
• 英文别名: N-(3,5-dichlorobenzenesulfonyl)-L-proline；N-(3,5-dichlorobenzenesulfonyl)-proline；N-(3,5-dichlorobenzenesulfonyl)-(L)-proline；N-(3,5-dichlorobenzenesulphonyl)-L-proline；(2S)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carboxylic Acid
• CAS: 217326-48-2
• 化学式: C₁₁H₁₁Cl₂NO₄S
• mdl: MFCD06858482
• 分子量: 324.185
• InChiKey: SRQOBFXQILTASR-JTQLQIEISA-N

物化性质

• 沸点：
  526.6±60.0 °C(Predicted)
• 密度：
  1.595±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3,5-二氯苯磺酰基)-l-脯氨酸 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (S)-2-{[(S)-1-(3,5-Dichloro-benzenesulfonyl)-pyrrolidine-2-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acid methyl ester
  参考文献：
  名称：

  The discovery of small molecule carbamates as potent dual α4β1/α4β7 integrin antagonists

  摘要：

  The alpha(4)beta(1) and alpha(4)beta(7) integrins are implicated in several inflammatory disease states. Systematic SAR studies of an alpha(4)beta(1)-specific arylsulfonyl-Pro-Tyr lead led to the identification of a new alpha(4)beta(7) binding site, best captured by O-carbamates of Tyr for this structural class. Several compounds showed a 200- to 400-fold improvement in alpha(4)beta(7) binding affinity while maintaining subnanomolar alpha(4)beta(1) activity, for example 21, VCAM-Ig alpha(4)beta(1) IC50 = 0.13 nM. VCAM-Ig alpha(4)beta(7) IC50 = 1.92 nM. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00710-7
• 作为产物：
  描述：

  3,5-二氯苯磺酰氯 在 吡啶 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 N-(3,5-二氯苯磺酰基)-l-脯氨酸
  参考文献：
  名称：

  Discovery of Proline Sulfonamides as Potent and Selective Hepatitis C Virus NS5b Polymerase Inhibitors. Evidence for a New NS5b Polymerase Binding Site

  摘要：

  Through high throughput screening, substituted proline sulfonamide 6 was identified as HCV NS5b RNA-dependent RNA polymerase inhibitor. Optimization of various regions of the lead molecule resulted in compounds that displayed good potency and selectivity. The crystal structure of 6 and NS5b polymerase complex confirmed the binding near the active site region. The optimization approach and SAR are discussed in detail.

  DOI：

  10.1021/jm060168g

文献信息

• Influence of acid surrogates toward potency of VLA-4 antagonist
  作者：Shankar Venkatraman、Jongwon Lim、Merryl Cramer、Michael F. Gardner、Joyce James、Kenneth Alves、Russell B. Lingham、Richard A. Mumford、Benito Munoz

  DOI：10.1016/j.bmcl.2005.06.034

  日期：2005.9

  A series of VLA-4 antagonist were synthesized wherein carboxylic acid was replaced by various acid surrogates. The effect of these acid surrogates toward potency was evaluated in a binding assay. A number of acid surrogates were potent antagonist of VLA-4, albeit significantly less potent than the corresponding carboxylic acid. Heterocyclic acid surrogate, oxadiazolidinone 3, demonstrated an improved

  合成了一系列VLA-4拮抗剂，其中用各种酸代用品代替羧酸。在结合试验中评估了这些酸代用品对效能的影响。许多酸替代物是VLA-4的有效拮抗剂，尽管其效力远低于相应的羧酸。当静脉内给药时，杂环酸替代物恶二唑烷酮3表现出改善的药代动力学性质。
• β-alanine derivates
  申请人：Porter John Robert

  公开号：US06953798B1

  公开（公告）日：2005-10-11

  Alkanoic acid derivatives of formula (1) are described: Ar 1 (Alk a ) r L 1 Ar 2 CH(R 1 )C(R a )(R a′ )R  (1) Ar 1 is an optionally substituted aromatic or heteroarotic group; L 1 is a covalent bond or a linker atom or group; Ar 2 is an optionally substituted phenylene or nitrogen-containing six-membered heteroarylene group; R is a carboxylic acid (—CO 2 H) or a derivative thereof; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of α4 integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders.

  公式（1）中描述了Alkanoic酸衍生物：Ar1(Alka)rL1Ar2CH(R1)C(Ra)(Ra′)R  (1)Ar1是一个可选择取代的芳香族或杂环芳基；L1是一个共价键或连接原子或基团；Ar2是一个可选择取代的苯基或含氮的六元杂环芳基；R是一个羧酸（—CO2H）或其衍生物；以及它们的盐、溶剂合物、水合物和N-氧化物。这些化合物能够抑制α4整合素与其配体的结合，并用于预防和治疗免疫或炎症性疾病。
• Cell adhesion inhibitors
  申请人：Lee Wen-Cherng

  公开号：US20060014966A1

  公开（公告）日：2006-01-19

  Cell adhesion inhibitors can interact with VLA-4 molecules and inhibits VLA-4 dependent cell adhesion. An inhibitor including a polyethylene glycol moiety can have advantageous pharmaceutical properties.

  细胞黏附抑制剂可以与VLA-4分子相互作用并抑制VLA-4依赖的细胞黏附。包括聚乙二醇基团的抑制剂可以具有优越的药物特性。
• [EN] HETEROCYCLIC AMIDE COMPOUNDS AS CELL ADHESION INHIBITORS<br/>[FR] COMPOSES D'AMIDE HETEROCYCLIQUES UTILISES EN TANT QU'INHIBITEURS DE L'ADHESION CELLULAIRE
  申请人：MERCK & CO., INC.

  公开号：WO1998053814A1

  公开（公告）日：1998-12-03

  (EN) Compounds of formula (I) are antagonists of VLA-4 and/or $g(a)4$g(b)7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of asthma, allergies, inflammation, multiple sclerosis, and other inflammatory and autoimmune disorders.(FR) Des composés de formule (I) sont des antagonistes de VLA-4 et/ou de $g(a)4$g(b)7 et sont, en tant que tels, utiles pour inhiber ou empêcher l'adhésion cellulaire et pour lutter contre des pathologies induites par l'adhésion cellulaire. Ces composés peuvent être formulés sous forme de compositions pharmaceutiques et sont adaptés pour être utilisés dans le traitement de l'asthme, des allergies, des inflammations, de la sclérose en plaques et d'autres maladies inflammatoires et auto-immunes.

  化合物的公式(I)是VLA-4和/或$g(a)4$g(b)7的拮抗剂，因此可用于抑制或预防细胞黏附和细胞黏附介导的病理反应。这些化合物可以制成药物组合物，适用于治疗哮喘、过敏、炎症、多发性硬化症和其他炎症和自身免疫性疾病。
• [EN] HETEROCYCLIC AMIDES WITH ALPHA-4 INTEGRIN ANTAGONIST ACTIVITY<br/>[FR] AMIDES HETEROCYCLIQUES A ACTIVITE ANTAGONISTE DE L'ALPHA-4 INTEGRINE
  申请人：URIACH & CIA SA J

  公开号：WO2003084984A1

  公开（公告）日：2003-10-16

  The present invention relates to new compounds of Formula (I) and the salts, solvates and prodrugs thereof, wherein the meanings for the various substituents are as disclosed in the description. These compounds are useful as integrin α4 antagonists.

  本发明涉及公式（I）的新化合物及其盐，溶剂合物和前药，其中各取代基的含义如描述中所披露。这些化合物可用作整合素α4拮抗剂。