{10-[4-(1-Methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-furan-3-yl]-6,7,8,9-tetrahydro-pyrido[1,2-a]indol-7-yl}-carbamic acid tert-butyl ester | 131849-34-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: {10-[4-(1-Methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-furan-3-yl]-6,7,8,9-tetrahydro-pyrido[1,2-a]indol-7-yl}-carbamic acid tert-butyl ester
• 英文别名: 3-[7-t-Butoxyformamido-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-methyl-3-indolyl)furan-2,5-dione；tert-butyl N-[10-[4-(1-methylindol-3-yl)-2,5-dioxofuran-3-yl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-7-yl]carbamate
• CAS: 131849-34-8
• 化学式: C₃₀H₂₉N₃O₅
• 分子量: 511.577
• InChiKey: OPKADJJTFNTGFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  91.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  {10-[4-(1-Methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-furan-3-yl]-6,7,8,9-tetrahydro-pyrido[1,2-a]indol-7-yl}-carbamic acid tert-butyl ester 在 盐酸 、 甲醇 、 六甲基二硅氮烷 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 3-[7-amino-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione hydrochloride
  参考文献：
  名称：

  Inhibitors of protein kinase C. 3. Potent and highly selective bisindolylmaleimides by conformational restriction

  摘要：

  The protein kinase inhibitor staurosporine has been used to design a series of selective bisindolylmaleimide inhibitors of protein kinase C (PKC). Guided by molecular graphics, conformational restriction of the cationic side chain has led to ATP competitive inhibitors of improved potency and selectivity. Two compounds have been further evaluated and were shown to inhibit PKC of human origin and prevent T-cell activation in a human allogeneic mixed lymphocyte reaction. One of these compounds was orally absorbed in mice and antagonized a phorbol ester induced paw edema in a dose-dependent manner. This compound also selectively inhibited the secondary T-cell mediated response in a developing adjuvant arthritis model in rats and provides evidence for the potential use of PKC inhibitors as therapeutic immunomodulators.

  DOI：

  10.1021/jm00053a003
• 作为产物：
  描述：

  7-tert.butoxyformamido-6,7,8,9-tetrahydropyrido<1,2-a>indole 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 70.08h， 生成 {10-[4-(1-Methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-furan-3-yl]-6,7,8,9-tetrahydro-pyrido[1,2-a]indol-7-yl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Inhibitors of protein kinase C. 3. Potent and highly selective bisindolylmaleimides by conformational restriction

  摘要：

  The protein kinase inhibitor staurosporine has been used to design a series of selective bisindolylmaleimide inhibitors of protein kinase C (PKC). Guided by molecular graphics, conformational restriction of the cationic side chain has led to ATP competitive inhibitors of improved potency and selectivity. Two compounds have been further evaluated and were shown to inhibit PKC of human origin and prevent T-cell activation in a human allogeneic mixed lymphocyte reaction. One of these compounds was orally absorbed in mice and antagonized a phorbol ester induced paw edema in a dose-dependent manner. This compound also selectively inhibited the secondary T-cell mediated response in a developing adjuvant arthritis model in rats and provides evidence for the potential use of PKC inhibitors as therapeutic immunomodulators.

  DOI：

  10.1021/jm00053a003

文献信息

• 4-\x9b3-indolyl!-1H-pyrrolone
  申请人：Hoffmann-La Roche Inc.

  公开号：US05721245A1

  公开（公告）日：1998-02-24

  A compound of the formula ##STR1## wherein R is hydrogen or hydroxy, R.sup.1 and R.sup.2 taken together are a group of the formula --(CH.sub.2).sub.m -- and R.sup.7 is hydrogen or R.sup.1 and R.sup.7 taken together are a group of the formula --(CH.sub.2).sub.n -- and R.sup.2 is hydrogen; R.sup.3 is an aryl or aromatic heterocyclic group; R.sup.4, R.sup.5 and R.sup.6 each independently are hydrogen, halogen, alkyl, hydroxy, alkoxy, haloalkyl, nitro, amino, acylamino, alkylthio, alkylsulfinyl or alkylsulfonyl; R.sup.8 is a group of the formula --(CH.sub.2).sub.p --R.sup.9 or --(CH.sub.2).sub.q --R.sup.10 ; R.sup.9 is hydrogen, alkylcarbonyl, aminoalkylcarbonyl, cyano, amidino, alkoxycarbonyl, aryloxycarbonyl, alkylsulfonyl, aminocarbonyl or aminothiocarbonyl; R.sup.10 is hydroxy, alkoxy, halogen, amino, monoalkylamino, dialkylamino, trialkylamino, azido, acylamino, alkylsulfonylamino, a 5- or 6-membered saturated nitrogen-containing heterocycle; X and Y are oxygen; Z is CH; m, p and q are, independently, an integer from 0 to 5, and n an integer from 1 to 5, as well as pharmaceutically acceptable salts thereof which are useful in the control of inflammatory, immunological, oncological, bronchopulmonary or cardiovascular disorders.

  化合物的公式为 ##STR1## 其中 R 是氢或羟基，R.sup.1 和 R.sup.2 结合在一起是一个公式为 --(CH.sub.2).sub.m -- 的基团，R.sup.7 是氢或 R.sup.1 和 R.sup.7 结合在一起是一个公式为 --(CH.sub.2).sub.n -- 的基团，R.sup.2 是氢；R.sup.3 是芳基或芳香杂环基；R.sup.4、R.sup.5 和 R.sup.6 分别独立地是氢、卤素、烷基、羟基、烷氧基、卤代烷基、硝基、氨基、酰胺基、烷基硫基、烷基亚磺酰基或烷基磺酰基；R.sup.8 是公式 --(CH.sub.2).sub.p --R.sup.9 或 --(CH.sub.2).sub.q --R.sup.10 的基团；R.sup.9 是氢、烷基羰基、氨基烷基羰基、氰基、酰胺基、烷氧基羰基、芳氧基羰基、烷基磺酰基、氨基羰基或氨基硫代羰基；R.sup.10 是羟基、烷氧基、卤素、氨基、单烷基氨基、双烷基氨基、三烷基氨基、偶氮基、酰胺基、烷基磺酰氨基、含氮的5-或6-元环饱和杂环；X 和 Y 是氧；Z 是 CH；m、p 和 q 分别是从 0 到 5 的整数，n 是从 1 到 5 的整数，以及其药学上可接受的盐，其在控制炎症、免疫、肿瘤、支气管肺部或心血管疾病中有用。
• Substituierte Pyrrole
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0384349A1

  公开（公告）日：1990-08-29

  Die Pyrrolderivate der Formel worin R¹ bis R⁸, R, X, Y und m die in der Beschreibung angegebene Bedeutung haben, sind therapeutisch aktive Sub­stanzen, insbesondere zur Verwendung als antiinflamma­torisch, immunologisch, onkologisch, bronchopulmonär und kardiovaskulär aktive Substanzen oder als Wirkstoffe in der Behandlung von Asthma oder AIDS. Sie werden hergestellt aus entsprechenden Furandion­derivaten, worin O für =N-R, X und Y steht.

  式中的吡咯衍生物 其中 R¹ 至 R⁸、R、X、Y 和 m 具有说明中给出的含义，是具有治疗活性的物质，特别是可用作抗炎、免疫、肿瘤、支气管和心血管活性物质或治疗哮喘或艾滋病的活性物质。 它们由相应的呋喃二酮衍生物制得，其中 O 代表 =N-R、X 和 Y。
• US5721245A
  申请人：——

  公开号：US5721245A

  公开（公告）日：1998-02-24
• Inhibitors of protein kinase C. 3. Potent and highly selective bisindolylmaleimides by conformational restriction
  作者：Rino A. Bit、Peter D. Davis、Lucy H. Elliott、William Harris、Christopher H. Hill、Elizabeth Keech、Hari Kumar、Geoffrey Lawton、Anna Maw、John S. Nixon、David R. Vesey、Julie Wadsworth、Sandra E. Wilkinson

  DOI：10.1021/jm00053a003

  日期：1993.1

  The protein kinase inhibitor staurosporine has been used to design a series of selective bisindolylmaleimide inhibitors of protein kinase C (PKC). Guided by molecular graphics, conformational restriction of the cationic side chain has led to ATP competitive inhibitors of improved potency and selectivity. Two compounds have been further evaluated and were shown to inhibit PKC of human origin and prevent T-cell activation in a human allogeneic mixed lymphocyte reaction. One of these compounds was orally absorbed in mice and antagonized a phorbol ester induced paw edema in a dose-dependent manner. This compound also selectively inhibited the secondary T-cell mediated response in a developing adjuvant arthritis model in rats and provides evidence for the potential use of PKC inhibitors as therapeutic immunomodulators.