1,3-dibutyl-7-phenylmethanesulfonyl-3,7-dihydro-purine-2,6-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 1,3-dibutyl-7-phenylmethanesulfonyl-3,7-dihydro-purine-2,6-dione
• 英文别名: 7-Benzylsulfonyl-1,3-dibutylpurine-2,6-dione
• 化学式: C₂₀H₂₆N₄O₄S
• 分子量: 418.517
• InChiKey: DZFTVPIHZOONHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,3-二-正-丁基黄嘌呤 、 苄磺酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以56%的产率得到1,3-dibutyl-7-phenylmethanesulfonyl-3,7-dihydro-purine-2,6-dione
  参考文献：
  名称：

  Novel and Selective Calcitonin-Inducing Agents

  摘要：

  A series of xanthine sulfonamides is presented as a class of calcitonin (CT) inducers - a potentially new method for treating diseases associated with postmenopausal bone loss such as osteoporosis. We have found that certain di-n-butylxanthine sulfonamides 4 upregulate CT transcription in a CT-luciferase reporter gene assay (CT-luci) and increase the production and release of CT in a CT secretion/RIA assay (CTS). In addition, these compounds do not have potent PDE4 inhibitory activity as do the related xanthine methylene ketones such as denbufyllene (2). One compound in particular (9) shows a transcription activation ratio (TAR) of 2.1 in CT-luci, a CTS increase of 3.6-fold, and a PDE4 (phosphodiesterase type IV) IC50 = 4.1 mu M. In addition, this compound showed a statistically significant 47% trabecular bone protection in ovariectomized-induced osteopenia (OVX) rats as determined by assay when administered for 4 weeks at 30 mg/kg/day, i.p. by quantitative computed tomography (QCT). When administered p.o., compound 9 shows 50% trabecular bone protection when administered for 3 weeks at 50 mg/kg/day, i.p. This compared with salmon CT which shows 62% trabecular bone protection when administered at 50 IU/kg/day for 4 weeks.

  DOI：

  10.1021/jm990558l

文献信息

• US6221874B1
  申请人：——

  公开号：US6221874B1

  公开（公告）日：2001-04-24
• Novel and Selective Calcitonin-Inducing Agents
  作者：Adam M. Gilbert、Stephen Caltabiano、Denise Roberts、Sam F. W. Sum、Gerardo D. Francisco、Kitae Lim、Magda Asselin、John W. Ellingboe、Yogendra Kharode、Anna Cannistraci、Rita Francis、Mark TrailSmith、David Gralnick

  DOI：10.1021/jm990558l

  日期：2000.3.1

  A series of xanthine sulfonamides is presented as a class of calcitonin (CT) inducers - a potentially new method for treating diseases associated with postmenopausal bone loss such as osteoporosis. We have found that certain di-n-butylxanthine sulfonamides 4 upregulate CT transcription in a CT-luciferase reporter gene assay (CT-luci) and increase the production and release of CT in a CT secretion/RIA assay (CTS). In addition, these compounds do not have potent PDE4 inhibitory activity as do the related xanthine methylene ketones such as denbufyllene (2). One compound in particular (9) shows a transcription activation ratio (TAR) of 2.1 in CT-luci, a CTS increase of 3.6-fold, and a PDE4 (phosphodiesterase type IV) IC50 = 4.1 mu M. In addition, this compound showed a statistically significant 47% trabecular bone protection in ovariectomized-induced osteopenia (OVX) rats as determined by assay when administered for 4 weeks at 30 mg/kg/day, i.p. by quantitative computed tomography (QCT). When administered p.o., compound 9 shows 50% trabecular bone protection when administered for 3 weeks at 50 mg/kg/day, i.p. This compared with salmon CT which shows 62% trabecular bone protection when administered at 50 IU/kg/day for 4 weeks.