[5-(2-Hydroxypropan-2-yl)-1,3-thiazol-2-yl]-(4-methylsulfonylphenyl)methanone | 346629-66-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [5-(2-Hydroxypropan-2-yl)-1,3-thiazol-2-yl]-(4-methylsulfonylphenyl)methanone
• CAS: 346629-66-1
• 化学式: C₁₄H₁₅NO₄S₂
• 分子量: 325.409
• InChiKey: QHOXPDXDTUROHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [5-(2-Hydroxypropan-2-yl)-1,3-thiazol-2-yl]-(4-methylsulfonylphenyl)methanone 、 (3-bromobenzyl)(triphenyl)phosphonium bromide 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-{2-[(E)-2-(3-Bromo-phenyl)-1-(4-methanesulfonyl-phenyl)-vinyl]-thiazol-5-yl}-propan-2-ol
  参考文献：
  名称：

  Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: Structure–activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor

  摘要：

  The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein described. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of emesis to efficacy in several animal models. Typical optimized compounds from this series are potent inhibitors of PDE4 (IC50 < 1 nM) and also of LPS-induced TNF-alpha release in human whole blood (IC50 < 0.5 mu M). The same compounds are potent inhibitors of ovalbumin-induced bronchoconstriction in conscious guinea pigs (EC50 < 0.1 mg/kg ip) but require a dose of about 10 mg/kg po in the squirrel monkey to produce an emetic response. From this series of compounds, 23a (L-454,560) was identified as an optimized compound. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.036
• 作为产物：
  描述：

  [5-(1-Hydroxy-1-methyl-ethyl)-thiazol-2-yl]-(4-methylsulfanyl-phenyl)-methanone 在 Oxone 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 [5-(2-Hydroxypropan-2-yl)-1,3-thiazol-2-yl]-(4-methylsulfonylphenyl)methanone
  参考文献：
  名称：

  Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: Structure–activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor

  摘要：

  The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein described. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of emesis to efficacy in several animal models. Typical optimized compounds from this series are potent inhibitors of PDE4 (IC50 < 1 nM) and also of LPS-induced TNF-alpha release in human whole blood (IC50 < 0.5 mu M). The same compounds are potent inhibitors of ovalbumin-induced bronchoconstriction in conscious guinea pigs (EC50 < 0.1 mg/kg ip) but require a dose of about 10 mg/kg po in the squirrel monkey to produce an emetic response. From this series of compounds, 23a (L-454,560) was identified as an optimized compound. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.036

文献信息

• Substituted 8-arylquinoline phosphodiesterase-4 inhibitors
  申请人：——

  公开号：US20020143032A1

  公开（公告）日：2002-10-03

  Novel sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, 2-naphthalenesulfonic acid, hydrochloride acid, or benzenesulfonic acid salts of substituted 8-arylquinolines, wherein the aryl group at the 8-position contains a substituent substituted-alkenyl group, are PDE4 inhibitors.

  新型硫酸、甲磺酸、对甲苯磺酸、2-萘磺酸、盐酸或苯磺酸盐的取代8-芳基喹啉，其中8位的芳基基团包含一个取代烯丙基基团，是PDE4抑制剂。
• SUBSTITUTED 8-ARYLQUINOLINE PHOSPHODIESTERASE-4 INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1363635B1

  公开（公告）日：2009-04-15
• US6410563B1
  申请人：——

  公开号：US6410563B1

  公开（公告）日：2002-06-25
• US6740666B2
  申请人：——

  公开号：US6740666B2

  公开（公告）日：2004-05-25
• Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: Structure–activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor
  作者：Dwight Macdonald、Anthony Mastracchio、Hélène Perrier、Daniel Dubé、Michel Gallant、Patrick Lacombe、Denis Deschênes、Bruno Roy、John Scheigetz、Kevin Bateman、Chun Li、Laird A. Trimble、Stephen Day、Nathalie Chauret、Deborah A. Nicoll-Griffith、Jose M. Silva、Zheng Huang、France Laliberté、Susana Liu、Diane Ethier、Doug Pon、Eric Muise、Louise Boulet、Chi Chung Chan、Angela Styhler、Stella Charleson、Joseph Mancini、Paul Masson、David Claveau、Donald Nicholson、Mervyn Turner、Robert N. Young、Yves Girard

  DOI：10.1016/j.bmcl.2005.08.036

  日期：2005.12

  The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein described. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of emesis to efficacy in several animal models. Typical optimized compounds from this series are potent inhibitors of PDE4 (IC50 < 1 nM) and also of LPS-induced TNF-alpha release in human whole blood (IC50 < 0.5 mu M). The same compounds are potent inhibitors of ovalbumin-induced bronchoconstriction in conscious guinea pigs (EC50 < 0.1 mg/kg ip) but require a dose of about 10 mg/kg po in the squirrel monkey to produce an emetic response. From this series of compounds, 23a (L-454,560) was identified as an optimized compound. (c) 2005 Elsevier Ltd. All rights reserved.