(3R)-6-cyclohexyl-3-[3-({[(4-fluorophenyl)sulfonyl]amino}carbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid | 467434-27-1

• 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: (3R)-6-cyclohexyl-3-[3-({[(4-fluorophenyl)sulfonyl]amino}carbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid
• 英文别名: (3R)-6-cyclohexyl-3-[3-[(4-fluorophenyl)sulfonylcarbamoyl]-1,2,4-oxadiazol-5-yl]hexanoic acid
• CAS: 467434-27-1
• 化学式: C₂₁H₂₆FN₃O₆S
• 分子量: 467.518
• InChiKey: XDTAFUYYCGCJNO-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (3R)-6-cyclohexyl-3-[3-({[(4-fluorophenyl)sulfonyl]amino}carbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid 在 三乙胺 、 氯甲酸异丁酯 、 O-(三甲基硅)羟胺 、 甲醇 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以0.17 g的产率得到(3R)-6-Cyclohexyl-3-[3-({[(4-fluorophenyl)sulfonyl]amino}carbonyl)-1,2,4-oxadiazol-5-yl]-N-hydroxyhexanamide
  参考文献：
  名称：

  Potent and Selective Nonpeptidic Inhibitors of Procollagen C-Proteinase

  摘要：

  6-Cyclohexyl-N-hydroxy-3-(1,2,4-oxadiazol-5-yl)hexanamides were previously disclosed as inhibitors of procollagen C-proteinase (PCP) culminating in the identification of amide 1. Our objective was to discover a second inhibitor that would have improved affinity for PCP and to optimize properties for transepidermal delivery (TED) to intact skin. Further investigation of this template identified a number of potent PCP inhibitors (IC50 values of 2-6 nM) with improved TED flux. Sulfonamide 56 had excellent PCP enzyme activity when measured with a peptide substrate (K-i 8.7 nM) or with the endogenous substrate procollagen (IC50 3.4 nM) and demonstrates excellent selectivity over MMPs involved in wound healing (> 10 000-fold). In the fibroplasia model, 56 inhibited deposition of insoluble collagen by 76 +/- 2% at 10 mu M and was very effective at penetrating human skin in vitro with a TED flux of 1.5 mu g/cm(2)/h, which compares favorably with values for agents that are known to penetrate skin well in vivo. Based on this profile, 56 (UK-421,045) was selected as a candidate for further preclinical evaluation as a topically applied, dermal anti-scarring agent.

  DOI：

  10.1021/jm061010z
• 作为产物：
  描述：

  4-氟苯磺酰氯 在 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (3R)-6-cyclohexyl-3-[3-({[(4-fluorophenyl)sulfonyl]amino}carbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid
  参考文献：
  名称：

  Potent and Selective Nonpeptidic Inhibitors of Procollagen C-Proteinase

  摘要：

  6-Cyclohexyl-N-hydroxy-3-(1,2,4-oxadiazol-5-yl)hexanamides were previously disclosed as inhibitors of procollagen C-proteinase (PCP) culminating in the identification of amide 1. Our objective was to discover a second inhibitor that would have improved affinity for PCP and to optimize properties for transepidermal delivery (TED) to intact skin. Further investigation of this template identified a number of potent PCP inhibitors (IC50 values of 2-6 nM) with improved TED flux. Sulfonamide 56 had excellent PCP enzyme activity when measured with a peptide substrate (K-i 8.7 nM) or with the endogenous substrate procollagen (IC50 3.4 nM) and demonstrates excellent selectivity over MMPs involved in wound healing (> 10 000-fold). In the fibroplasia model, 56 inhibited deposition of insoluble collagen by 76 +/- 2% at 10 mu M and was very effective at penetrating human skin in vitro with a TED flux of 1.5 mu g/cm(2)/h, which compares favorably with values for agents that are known to penetrate skin well in vivo. Based on this profile, 56 (UK-421,045) was selected as a candidate for further preclinical evaluation as a topically applied, dermal anti-scarring agent.

  DOI：

  10.1021/jm061010z

文献信息

• 3-heterocyclylpropanohydroxamic acid PCP inhibitors
  申请人：——

  公开号：US20020187979A1

  公开（公告）日：2002-12-12

  Compounds of formula (I) 1 and their salts, solvates and prodrugs, wherein the substituents have the values mentioned herein, are Procollagen C-Proteinase (PCP) inhibitors and have utility in conditions mediated by PCP.

  化学式（I）1的化合物及其盐，溶剂合物和前药，其中取代基具有下列所述的值，是前胶原C蛋白酶（PCP）抑制剂，并在由PCP介导的疾病中具有用途。
• 3-Heterocyclylpropanohydroxamic acid PCP inhibitors
  申请人：——

  公开号：US20040058917A1

  公开（公告）日：2004-03-25

  Compounds of formula (I): 1 and their salts, solvates, prodrugs, etc., wherein the substituents have the values mentioned herein, are Procollagen C-Proteinase (PCP) inhibitors and have utility in conditions mediated by PCP.

  式(I)的化合物及其盐类、溶剂化物、前药等，其中取代基具有所述数值，是胶原原C-蛋白酶（PCP）抑制剂，可用于PCP介导的疾病。
• 3-HETEROCYCLYLPROPANOHYDROXAMIC ACID PCP INHIBITORS
  申请人：Pfizer Limited

  公开号：EP1373231A1

  公开（公告）日：2004-01-02
• 3-HETEROCYCLYL-PROPANO-HYDROXAMIC ACID AS PCP INHIBITORS
  申请人：Pfizer Limited

  公开号：EP1373231B1

  公开（公告）日：2005-06-08
• US6645993B2
  申请人：——

  公开号：US6645993B2

  公开（公告）日：2003-11-11