tert-butyl ((1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)methyl)carbamate | 885594-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: tert-butyl ((1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)methyl)carbamate
• 英文别名: [1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidin-4-ylmethyl]-carbamic acid tert-butyl ester；Carbamic acid,n-[[1-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidinyl]methyl]-,1,1-dimethylethyl ester；tert-butyl N-[[1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methyl]carbamate
• CAS: 885594-86-5
• 化学式: C₁₇H₂₅N₅O₂
• 分子量: 331.418
• InChiKey: QNPDJHFTYKKYKG-UHFFFAOYSA-N

物化性质

• 密度：
  1.198±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  83.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl ((1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)methyl)carbamate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 C-[1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidin-4-yl]-methylamine
  参考文献：
  名称：

  通过片段加工鉴定4-（4-氨基哌啶-1-基）-7H-吡咯并[2,3-d]嘧啶作为蛋白激酶B的选择性抑制剂。

  摘要：

  基于片段的筛选确定7-氮杂吲哚为蛋白激酶B抑制剂支架。使用抑制剂-PKA-PKB嵌合体复合物的反复结晶学方法对片段进行精细加工，可有效指导化合物效力和选择性的提高，从而鉴定出纳摩尔级的6-（哌啶-1-基）嘌呤，4-（哌啶-1-基）纳摩尔。 ）-7-氮杂吲哚和PKBbeta的4-（哌啶-1-基）吡咯并[2,3-d]嘧啶抑制剂具有抗增殖活性，并在细胞中表现出途径抑制作用。在包含4-氨基甲基哌啶和含4-氨基哌啶的分子之间观察到结合模式的差异。用4-氨基哌啶衍生物观察到PKB对PKA的选择性，大多数PKB选择性抑制剂（30倍）显示出PKA和PKA-PKB嵌合体之间的结合构象显着不同。

  DOI：

  10.1021/jm701437d
• 作为产物：
  描述：

  4-羟基吡咯并[2,3-d]嘧啶 在 三乙胺 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 5.5h， 生成 tert-butyl ((1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)methyl)carbamate
  参考文献：
  名称：

  WO2007/125315

  摘要：

  公开号：

文献信息

• Pharmaceutical Compounds
  申请人：Davies Thomas Glanmor

  公开号：US20090253718A1

  公开（公告）日：2009-10-08

  The invention provides a compound having the formula (I): or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR 5 ; J 1 -J 2 is N═C(R 6 ), (R 7 )C═N, (R 8 )N—C(O), (R 8 ) 2 C—C(O), N═N or (R 7 )C═C(R 6 ); A is an optionally substituted saturated C 1-7 hydrocarbon linker group having a maximum chain length of 5 atoms extending between R 1 and NR 2 R 3 and a maximum chain length of 4 atoms extending between E and NR 2 R 3 , one of the carbon atoms in the linker group being optionally replaced by oxygen or nitrogen; E is a monocyclic or bicyclic carbocyclic or heterocyclic group or an acyclic group X-G wherein X is CH 2 , O, S or NH and G is a C 1-4 alkylene chain wherein one of the carbon atoms is optionally replaced by O, S or NH; R 1 is hydrogen or an aryl or heteroaryl group; R 2 and R 3 are each hydrogen, optionally substituted C 1-4 hydrocarbyl or optionally substituted C 1-4 acyl; or NR 2 R 3 forms an imidazole group or a saturated monocyclic heterocyclic group having 4-7 ring members; or NR 2 R 3 and A together form a saturated monocyclic heterocyclic group having 4-7 ring members which is optionally substituted by C 1-4 alkyl; or NR 2 R 3 and the adjacent carbon atom of linker group A together form a cyano group; or R 1 , A and NR 2 R 3 together form a cyano group; and R 4 , R 5 , R 6 , R 7 and R 8 are each independently selected from hydrogen and various substituents as defined in the claims, wherein the compound is for use in: (a) the treatment or prophylaxis of a disease or condition in which the modulation (e.g. inhibition) of ROCK kinase or protein kinase p70S6K is indicated; and/or (b) the treatment of a subject or patient population in which the modulation (e.g. inhibition) of ROCK kinase or protein kinase p70S6K is indicated.

  本发明提供了具有以下式子（I）的化合物或其盐，溶剂化物，互变异构体或N-氧化物，其中T为N或CR5; J1-J2为N═C（R6），（R7）C═N，（R8）N—C（O），（R8）2C—C（O），N═N或（R7）C═C（R6）; A为最大链长为5个原子的选择性取代的饱和C1-7碳氢链连接基，在R1和NR2R3之间延伸，最大链长为4个原子，在E和NR2R3之间延伸，链连接基中的一个碳原子可以被氧或氮取代; E为单环或双环的碳环或杂环基团或一个无环的X-G基团，其中X为CH2，O，S或NH，G为一个C1-4烷基链，其中一个碳原子可以被O，S或NH取代; R1为氢或芳基或杂环基团; R2和R3分别为氢，选择性取代的C1-4烃基或选择性取代的C1-4酰基; 或NR2R3形成咪唑基团或具有4-7个环成员的饱和单环杂环基团; 或NR2R3和A一起形成一个被C1-4烷基取代的饱和单环杂环基团; 或NR2R3和链连接基A的相邻碳原子一起形成氰基团; 或R1，A和NR2R3一起形成氰基团; R4，R5，R6，R7和R8各自独立地选择氢和各种在权利要求中定义的取代基，其中该化合物用于：（a）治疗或预防调节ROCK激酶或蛋白激酶p70S6K所示的疾病或情况; 和/或（b）治疗调节ROCK激酶或蛋白激酶p70S6K所示的受试者或患者人群。
• Ortho-Condensed Pyridine and Pyrimidine Derivatives (e.g., Purines) as Protein Kinases Inhibitors
  申请人：Berdini Valerio

  公开号：US20090099213A1

  公开（公告）日：2009-04-16

  The invention provides a compound for use in the prophylaxis or treatment of a disease state or condition mediated by protein kinase B, the compound having the formula (I): or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR 5 ; J 1 -J 2 is N═C(R 6 ), (R 7 )C═N, (R 8 )N—C(O), (R 8 ) 2 C—C(O), N═N or (R 7 )C═C(R 6 ); A is an optionally substituted saturated C 1-7 hydrocarbon linker group having a maximum chain length of 5 atoms extending between R 1 and NR 2 R 3 and a maximum chain length of 4 atoms extending between E and NR 2 R 3 , one of the carbon atoms in the linker group being optionally replaced by oxygen or nitrogen; E is a monocyclic or bicyclic carbocyclic or heterocyclic group or an acyclic group X-G wherein X is CH 2 , O, S or NH and G is a C 1-4 alkylene chain wherein one of the carbon atoms is optionally replaced by O, S or NH; R 1 is hydrogen or an aryl or heteroaryl group; R 2 and R 3 are each hydrogen, optionally substituted C 1-4 hydrocarbyl or optionally substituted C 1-4 acyl; or NR 2 R 3 forms an imidazole group or a saturated monocyclic heterocyclic group having 4-7 ring members; or NR 2 R 3 and A together form a saturated monocyclic heterocyclic group having 4-7 ring members which is optionally substituted by C 1-4 alkyl; or NR 2 R 3 and the adjacent carbon atom of linker group A together form a cyano group; or R 1 , A and NR 2 R 3 together form a cyano group; and R 4 , R 5 , R 6 , R 7 and R 8 are each independently selected from hydrogen and various substituents as defined in the claims.

  本发明提供了一种化合物，可用于预防或治疗由蛋白激酶B介导的疾病状态或病况，该化合物具有以下式（I）或其盐，溶剂化合物，互变异构体或N-氧化物，其中T为N或CR5；J1-J2为N═C（R6），（R7）C═N，（R8）N—C（O），（R8）2C—C（O），N═N或（R7）C═C（R6）；A为一个可选取代的饱和C1-7碳链连接基团，其最大链长为5个原子，延伸在R1和NR2R3之间，并且最大链长为4个原子，延伸在E和NR2R3之间，连接基团中的一个碳原子可被氧或氮取代；E为单环或双环碳环或杂环基团或一个无环基团X-G，其中X为CH2，O，S或NH，G为C1-4烷基链，其中一个碳原子可被O，S或NH取代；R1为氢或芳基或杂芳基团；R2和R3分别为氢，可选取代的C1-4烃基或可选取代的C1-4酰基；或NR2R3形成咪唑基团或具有4-7个环成员的饱和单环杂环基团；或NR2R3和A一起形成具有4-7个环成员的饱和单环杂环基团，该基团可选取代为C1-4烷基；或NR2R3和连接基团A的相邻碳原子一起形成氰基团；或R1，A和NR2R3一起形成氰基团；R4，R5，R6，R7和R8各自独立地选择氢和各种定义中定义的取代基。
• Identification of novel pyrrolopyrimidine and pyrrolopyridine derivatives as potent ENPP1 inhibitors
  作者：Hee Jin Jeong、Hye Lim Lee、Sung Joon Kim、Jeong Hyun Jeong、Su Hyun Ji、Han Byeol Kim、Miso Kang、Hwan Won Chung、Chan Sun Park、Hyunah Choo、Hyo Jae Yoon、Nam-Jung Kim、Duck-Hyung Lee、Sanghee Lee、Seo-Jung Han

  DOI：10.1080/14756366.2022.2119566

  日期：2022.12.31

  Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibitors to stimulate the Stimulator of Interferon Genes (STING) pathway, we designed and synthesised pyrrolopyrimidine and pyrrolopyridine derivatives and performed structure-activity relationship (SAR) study. We found 18p possessed high potency (IC50 = 25.0 nM) against ENPP1, and activated STING pathway in a concentration dependent manner

  摘要 为了发现新的非核苷酸衍生的外核苷酸焦磷酸酶/磷酸二酯酶 1 (ENPP1) 抑制剂支架以刺激干扰素基因刺激物 (STING) 途径，我们设计并合成了吡咯并嘧啶和吡咯并吡啶衍生物，并进行了构效关系 (SAR ） 学习。我们发现18p对 ENPP1具有高效力 (IC 50 = 25.0 nM)，并以浓度依赖性方式激活 STING 途径。此外，响应 STING 通路激活， 18p以浓度依赖性方式诱导细胞因子如 IFN- β和 IP-10。最后，我们发现18p在 4T1 同基因小鼠模型中抑制肿瘤生长。这项研究为新型 ENPP1 抑制剂的设计提供了新的见解，并保证了进一步开发用于癌症免疫治疗的小分子免疫调节剂。
• WO2006/46023
  申请人：——

  公开号：——

  公开（公告）日：——
• PYRROLOPYRIMIDINE DERIVATIVE HAVING ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE INHIBITORY ACTIVITY AND USE THEREOF
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US20220411420A1

  公开（公告）日：2022-12-29

  Disclosed is a novel pyrrolopyrimidine derivative compound, a tautomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a stereoisomer thereof, associated with a compound for inhibiting ENPP1, a composition for inhibiting ENPP1, and a method of inhibiting ENPP1.