3-((S)-8-Hydroxymethyl-6,7,8,9-tetrahydro-pyrido[1,2-a]indol-10-yl)-4-phenylamino-pyrrole-2,5-dione | 257875-03-9

• 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
• 英文名称: 3-((S)-8-Hydroxymethyl-6,7,8,9-tetrahydro-pyrido[1,2-a]indol-10-yl)-4-phenylamino-pyrrole-2,5-dione
• 英文别名: 3-anilino-4-[(8S)-8-(hydroxymethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]pyrrole-2,5-dione
• CAS: 257875-03-9
• 化学式: C₂₃H₂₁N₃O₃
• 分子量: 387.438
• InChiKey: XKPHPTHLQNGXJQ-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  83.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-((S)-8-Hydroxymethyl-6,7,8,9-tetrahydro-pyrido[1,2-a]indol-10-yl)-4-phenylamino-pyrrole-2,5-dione 在 吡啶 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 18.0h， 生成 3-((S)-8-Dimethylaminomethyl-6,7,8,9-tetrahydro-pyrido[1,2-a]indol-10-yl)-4-phenylamino-pyrrole-2,5-dione
  参考文献：
  名称：

  Synthesis, SAR studies, and pharmacological evaluation of 3-anilino-4-(3-indolyl) maleimides with conformationally restricted structure as orally bioavailable PKCβ-selective inhibitors

  摘要：

  Conformationally restricted 3-anilino-4-(3-indolyl)maleimide derivatives were designed and synthesized aiming at discovery of novel protein kinase C beta (PKC beta)-selective inhibitors possessing oral bioavailability. Among them, compounds having a fused five-membered ring at the indole 1,2-position inhibited PKC beta 2 with IC50 of nM-order and showed good oral bioavailability. One of the most potent compounds was found to be PKC beta-selective over other 6 isozymes and exhibited ameliorative effects in a rat diabetic retinopathy model via oral route. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.05.033
• 作为产物：
  描述：

  3-[(S)-8-(tert-Butyl-diphenyl-silanyloxymethyl)-6,7,8,9-tetrahydro-pyrido[1,2-a]indol-10-yl]-4-phenylamino-pyrrole-2,5-dione 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以97%的产率得到3-((S)-8-Hydroxymethyl-6,7,8,9-tetrahydro-pyrido[1,2-a]indol-10-yl)-4-phenylamino-pyrrole-2,5-dione
  参考文献：
  名称：

  Synthesis, SAR studies, and pharmacological evaluation of 3-anilino-4-(3-indolyl) maleimides with conformationally restricted structure as orally bioavailable PKCβ-selective inhibitors

  摘要：

  Conformationally restricted 3-anilino-4-(3-indolyl)maleimide derivatives were designed and synthesized aiming at discovery of novel protein kinase C beta (PKC beta)-selective inhibitors possessing oral bioavailability. Among them, compounds having a fused five-membered ring at the indole 1,2-position inhibited PKC beta 2 with IC50 of nM-order and showed good oral bioavailability. One of the most potent compounds was found to be PKC beta-selective over other 6 isozymes and exhibited ameliorative effects in a rat diabetic retinopathy model via oral route. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.05.033

文献信息

• Synthesis, SAR studies, and pharmacological evaluation of 3-anilino-4-(3-indolyl) maleimides with conformationally restricted structure as orally bioavailable PKCβ-selective inhibitors
  作者：Masahiro Tanaka、Shoichi Sagawa、Jun-ichi Hoshi、Fumito Shimoma、Katsutaka Yasue、Minoru Ubukata、Tomoyuki Ikemoto、Yasunori Hase、Mitsuru Takahashi、Tomohiko Sasase、Nobuhisa Ueda、Mutsuyoshi Matsushita、Takashi Inaba

  DOI：10.1016/j.bmc.2006.05.033

  日期：2006.9

  Conformationally restricted 3-anilino-4-(3-indolyl)maleimide derivatives were designed and synthesized aiming at discovery of novel protein kinase C beta (PKC beta)-selective inhibitors possessing oral bioavailability. Among them, compounds having a fused five-membered ring at the indole 1,2-position inhibited PKC beta 2 with IC50 of nM-order and showed good oral bioavailability. One of the most potent compounds was found to be PKC beta-selective over other 6 isozymes and exhibited ameliorative effects in a rat diabetic retinopathy model via oral route. (c) 2006 Elsevier Ltd. All rights reserved.