7-methyl-9-[(3-methylbenzyl)amino]-2-(4-morpholinyl)-4H-pyrido[1,2-a]pyrimidin-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 7-methyl-9-[(3-methylbenzyl)amino]-2-(4-morpholinyl)-4H-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: MCA51；7-Methyl-9-[(3-methylphenyl)methylamino]-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one
• 化学式: C₂₁H₂₄N₄O₂
• 分子量: 364.447
• InChiKey: XAGGIZNFVKTVJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-3-溴-5-甲基吡啶 在 potassium tert-butylate 、 palladium diacetate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 甲基磺酰氯 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 丙酮 为溶剂， 反应 26.0h， 生成 7-methyl-9-[(3-methylbenzyl)amino]-2-(4-morpholinyl)-4H-pyrido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  Exploring the isoform selectivity of TGX-221 related pyrido[1,2-a]pyrimidinone-based Class IA PI 3-kinase inhibitors: Synthesis, biological evaluation and molecular modelling

  摘要：

  A novel series of TGX-221 analogues was prepared and tested for their potency against the p110 alpha, p110 beta, and p110 delta isoforms of the PI3K enzyme, and in two cellular assays. The biological results were interpreted in terms of a p110 beta comparative model, in order to account for their selectivity towards this isoform. A CH2NH type linker is proposed to allow binding into the specificity pocket proposed to accommodate the high p110 beta-selectivity of TGX-221, although there was limited steric tolerance for substituents on the pendant ring with the 2-position most favourable for substitution. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.03.073

文献信息

• Methods of inhibiting leukocyte accumulation
  申请人：Diacovo G. Thomas

  公开号：US20050054614A1

  公开（公告）日：2005-03-10

  The invention relates generally to phosphoinositide 3-kinases (PI3Ks), and more particularly to methods of inhibiting leukocyte accumulation comprising selectively inhibiting phosphoinositide 3-kinase delta (PI3Kδ) activity in endothelial cells.

  本发明总体上涉及磷酸肌醇 3-激酶（PI3K），更具体地说，涉及通过选择性地抑制内皮细胞中磷酸肌醇 3-激酶δ（PI3Kδ）的活性来抑制白细胞聚集的方法。
• Methods for treating and/or preventing aberrant proliferation of hematopoietic cells
  申请人：Bouscary Didier

  公开号：US20060106038A1

  公开（公告）日：2006-05-18

  The invention relates generally to methods for treating and/or preventing aberrant proliferation of hematopoietic cells. More particularly, the invention relates to methods for treating and/or preventing aberrant proliferation of hematopoietic cells comprising selectively inhibiting phosphoinositide 3-kinase delta (PI3Kδ) activity in hematopoietic cells. The methods may be used to treat any indication involving aberrant proliferation of hematopoietic cells.

  本发明一般涉及治疗和/或预防造血细胞异常增殖的方法。更具体地说，本发明涉及治疗和/或预防造血细胞异常增殖的方法，包括选择性地抑制造血细胞中磷酸肌醇 3-激酶δ（PI3Kδ）的活性。这些方法可用于治疗任何涉及造血细胞异常增殖的病症。
• Isoform-specific phosphoinositide 3-kinase inhibitors from an arylmorpholine scaffold
  作者：Zachary A. Knight、Gary G. Chiang、Peter J. Alaimo、Denise M. Kenski、Caroline B. Ho、Kristin Coan、Robert T. Abraham、Kevan M. Shokat

  DOI：10.1016/j.bmc.2004.06.022

  日期：2004.9

  Phosphoinositide 3-kinases (PI3-Ks) are an ubiquitous class of signaling enzymes that regulate diverse cellular processes including growth, differentiation, and motility. Physiological roles of PI3-Ks have traditionally been assigned using two pharmacological inhibitors, LY294002 and wortmannin. Although these compounds are broadly specific for the PI3-K family, they show little selectivity among family members, and the development of isoform-specific inhibitors of these enzymes has been long anticipated. Herein, we prepare compounds from two classes of arylmorpholine PI3-K inhibitors and characterize their specificity against a comprehensive panel of targets within the PI3-K family. We identify multiplex inhibitors that potently inhibit distinct subsets of PI3-K isoforms, including the first selective inhibitor of p110beta/p110delta (IC50 p110beta = 0.13 muM, p110delta = 0.63 muM). We also identify trends that suggest certain PI3-K isoforms may be more sensitive to potent inhibition by arylmorpholines, thereby guiding future drug design based on this pharmacophore. (C) 2004 Elsevier Ltd. All rights reserved.
• PHOSPHOINOSITIDE 3-KINASE INHIBITORS FOR INHIBITING LEUKOCYTE ACCUMULATION
  申请人：ICOS CORPORATION

  公开号：EP1885356A2

  公开（公告）日：2008-02-13
• Methods of inhibiting immune responses stimulated by an endogenous factor
  申请人：Douangpanya Jason

  公开号：US20050043239A1

  公开（公告）日：2005-02-24

  The present invention relates generally to phosphoinositide 3-kinases (PI3Ks), and more particularly to methods of inhibiting undesirable immune responses without inhibiting desired immune responses. In one embodiment, the invention provides methods of inhibiting an endogenous immune response stimulated by at least one endogenous factor without substantially inhibiting an exogenous immune response stimulated by at least one exogenous factor comprising administering an amount of a phosphoinositide 3-kinase delta (PI3Kδ) selective inhibitor effective to inhibit the endogenous immune response stimulated by endogenous factor without substantially inhibiting the exogenous immune response stimulated by the at least one exogenous factor.