2-甲基-3H,4H-吡啶并[3,4-d]嘧啶-4-酮 | 22389-85-1

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 中文名称: 2-甲基-3H,4H-吡啶并[3,4-d]嘧啶-4-酮
• 中文别名: 2-甲基吡啶并[3,4-D]嘧啶-4(1H)-酮
• 英文名称: 2-methylpyrido<3,4-d>pyrimidin-4(3H)-one
• 英文别名: 2-methylpyrido[3,4-d]pyrimidin-4(3H)-one；2-Methyl-pyrido<3.4-d>pyrimidon-(4)；2-methyl-3H-pyrido[3,4-d]pyrimidin-4-one；2-Methyl-3H-pyrido[3,4-d]pyrimidin-4-on；2-Methylpyrido[3,4-d]pyrimidin-4(1H)-one；2-methyl-3H-pyrido[3,4-d]pyrimidin-4-one
• CAS: 22389-85-1
• 化学式: C₈H₇N₃O
• mdl: MFCD18836871
• 分子量: 161.163
• InChiKey: ZZGGQKRBGZEHKC-UHFFFAOYSA-N

物化性质

• 沸点：
  340.8±34.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-甲基-3H,4H-吡啶并[3,4-d]嘧啶-4-酮 在 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 乙醇 、 苯 为溶剂， 反应 18.5h， 生成 2-methyl-4-isoamylaminopyrido<3,4-d>pyrimidine
  参考文献：
  名称：

  Nishikawa, Shiro; Kumazawa, Zenzaburo; Kashimura, Naoki, Agricultural and Biological Chemistry, 1986, vol. 50, # 2, p. 495 - 498

  摘要：

  DOI：
• 作为产物：
  描述：

  2-甲基-4H-吡啶并[3,4-d] [1,3]恶嗪-4-酮 在 ammonium hydroxide 作用下， 反应 1.0h， 生成 2-甲基-3H,4H-吡啶并[3,4-d]嘧啶-4-酮
  参考文献：
  名称：

  Preparation and structure-activity relationships of 4-substituted amino-2-methylpyrido[3,4-d]pyrimidines as cytokinin analogs

  摘要：

  Various 4-substituted amino derivatives of 2-methylpyrido[3,4-d]pyrimidine were prepared to investigate their structure-cytokinin activity relationships. Both an Amaranthus betacyanin and a lettuce seed germination bioassay revealed that most anilino and some alkylamino derivatives were active, whereas benzylamino derivatives were inactive, indicating that the new cytokinin analogs differ from N-6-adenines in their substituent effects on the activity. The most active was a m-fluoroanilino derivative, which was as potent as N-6-benzyladenine in a tobacco callus bioassay. 2-Alkyl substituents smaller or larger than a methyl group reduced the activity.

  DOI：

  10.1021/jf00052a035

文献信息

• SUBSTITUTED 2- AMIDOQUINAZOL-4-ONES AS MATRIX METALLOPROTEINASE-13 INHIBITORS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20150329556A1

  公开（公告）日：2015-11-19

  The present invention provides a novel amide derivative having a matrix metalloproteinase inhibitory activity, and useful as a pharmaceutical agent, which is a compound represented by the formula (I) wherein ring A is an optionally substituted, nitrogen containing heterocycle, ring B is an optionally substituted monocyclic homocycle or an optionally substituted monocyclic heterocycle, Z is N or NR 1 (R 1 is a hydrogen atom or an optionally substituted hydrocarbon group), is a single bond or a double bond, R 2 is a hydrogen atom or an optionally substituted hydrocarbon group, X is an optionally substituted spacer having 1 to 6 atoms, ring C is (1) an optionally substituted homocycle or (2) an optionally substituted heterocycle other than a ring represented by (II) (X′ is S, O, SO, or CH 2 ), and at least one of ring B and ring C has substituent(s), provided that N-(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]2 hydroxypropyl}5,6 dimethyl 4 oxo 1,4 dihydrothieno[2,3-d]pyrimidine-2-carboxamide is excluded, or a salt thereof.

  本发明提供了一种新型酰胺衍生物，具有基质金属蛋白酶抑制活性，并且作为药用剂是有用的，该化合物由以下式(I)表示，其中环A是一个可选择取代的含氮杂环，环B是一个可选择取代的单环同核环或可选择取代的单环杂环，Z是N或NR1（R1是氢原子或可选择取代的碳氢基团），是一个单键或双键，R2是氢原子或可选择取代的碳氢基团，X是一个具有1到6个原子的可选择取代的间隔物，环C是（1）一个可选择取代的同核环或（2）一个除了由（II）表示的环之外的可选择取代的杂环（X′是S、O、SO或CH2），并且环B和环C中至少有一个有取代基，但不包括N-(1S,2R)-1-(3,5-二氟苄基)-3-[(3-乙基苄基)氨基]2-羟基丙基}5,6-二甲基-4-氧代-1,4-二氢噻唑并[2,3-d]嘧啶-2-羧酰胺，或其盐。
• [EN] HETEROCYCLIC AMIDE COMPOUND AND USE THEREOF AS AN MMP-13 INHIBITOR<br/>[FR] COMPOSÉ AMIDE HETEROCYCLIQUE ET UTILISATION DE CELUI-CI EN TANT QU'INHIBITEUR MMP-13
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2005105760A1

  公开（公告）日：2005-11-10

  The present invention provides a novel amide derivative having a matrix metalloproteinase inhibitory activity, and useful as a pharmaceutical agent, which is a compound represented by the formula (I) wherein ring A is an optionally substituted, nitrogen-containing heterocycle, ring B is an optionally substituted monocyclic homocycle or an optionally substituted monocyclic heterocycle, Z is N or NR1 (R1 is a hydrogen atom or an optionally substituted hydrocarbon group), - - - is a single bond or a double bond, R2 is a hydrogen atom or an optionally substituted hydrocarbon group, X is an optionally substituted spacer having 1 to 6 atoms, ring C is (1) an optionnally substituted homocycle or (2) an optionally substituted heterocycle other than a ring represented by (II) (X’ is S, O, SO, or CH2), and at least one of ring B and ring C has substituent(s), provided that N-(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5,6-dimethyl-4-oxo-1,4-dihadrothieno[2,3-d]pyrimidine-2-carboxamide is excluded, or a salt thereof.

  本发明提供了一种新型酰胺衍生物，具有基质金属蛋白酶抑制活性，并且作为药用剂是有用的，该化合物由以下式(I)表示，其中环A是一个可选择取代的含氮杂环，环B是一个可选择取代的单环同核环或可选择取代的单环杂环，Z是N或NR1（R1是氢原子或可选择取代的碳氢基团），- - - 是一个单键或双键，R2是氢原子或可选择取代的碳氢基团，X是具有1到6个原子的可选择取代的间隔物，环C是(1)一个可选择取代的同核环或(2)除了由(II)表示的环之外的可选择取代的杂环（X'是S、O、SO或CH2），并且环B和环C中至少有一个具有取代基，但不包括N-(1S,2R)-1-(3,5-二氟苄基)-3-[(3-乙基苄基)氨基]-2-羟基丙基}-5,6-二甲基-4-氧代-1,4-二氢噻吩[2,3-d]嘧啶-2-羧酰胺或其盐。
• [EN] HISTONE DEMETHYLASE INHIBITORS<br/>[FR] INHIBITEURS DE L'HISTONE DÉMÉTHYLASE
  申请人：QUANTICEL PHARMACEUTICALS INC

  公开号：WO2016044429A1

  公开（公告）日：2016-03-24

  The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyrido[3,4-d]pyrimidin-4-one derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

  本发明通常涉及治疗癌症和肿瘤性疾病的组合物和方法。本文提供了替代的吡啶并[3,4-d]嘧啶-4-酮衍生物化合物和包含该化合物的药物组合物。所述化合物和组合物对组蛋白去甲基化酶的抑制有用。此外，所述化合物和组合物对于治疗癌症，如前列腺癌、乳腺癌、膀胱癌、肺癌和/或黑色素瘤等方面是有用的。
• Pyrido[3,4-<i>d</i>]pyrimidin-4(3<i>H</i>)-one metabolism mediated by aldehyde oxidase is blocked by C2-substitution
  作者：Angela Hayes、N. Yi Mok、Manjuan Liu、Ching Thai、Alan T. Henley、Butrus Atrash、Rachel M. Lanigan、Jimmy Sejberg、Yann-Vaï Le Bihan、Vassilios Bavetsias、Julian Blagg、Florence I. Raynaud

  DOI：10.1080/00498254.2016.1230245

  日期：2017.9.2

  C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one derivatives as cell permeable inhibitors of the KDM4 and KDM5 subfamilies of JmjC histone lysine demethylases. 2. Although exemplar compound 1 exhibited moderate clearance in mouse liver microsomes, it was highly cleared in vivo due to metabolism by aldehyde oxidase (AO). Similar human and mouse AO-mediated metabolism was observed with the pyrido[3,4-d]pyrimidin-4(3H)-one

  1. 我们之前已经描述了 C8 取代的吡啶并[3,4- d ]嘧啶-4(3 H )-one 衍生物作为 JmjC 组蛋白赖氨酸脱甲基酶 KDM4 和 KDM5 亚家族的细胞渗透性抑制剂。 2.尽管示例化合物1在小鼠肝微粒体中表现出中等清除率，但由于醛氧化酶(AO)的代谢，其在体内被高度清除。使用吡啶并[3,4- d ]嘧啶-4(3H ) -one支架和其他C8取代衍生物观察到类似的人和小鼠AO介导的代谢。 3.我们通过LC-MS和1 H-NMR鉴定出C2位为氧化位点，并表明C2取代的衍生物不再是AO底物。 4. 除了实验数据之外，这些观察结果还得到了人类 AO 蛋白晶体结构的分子模型研究的支持。
• [EN] AZAQUINAZOLINE INHIBITORS OF ATYPICAL PROTEIN KINASE C<br/>[FR] INHIBITEURS DE TYPE AZAQUINAZOLINE DE PROTÉINE KINASE C ATYPIQUE
  申请人：IGNYTA INC

  公开号：WO2014052699A9

  公开（公告）日：2015-07-16