5-fluoro-4-methyl-2-pyridin-2-yl-1H-pyrimidin-6-one | 1431331-23-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-fluoro-4-methyl-2-pyridin-2-yl-1H-pyrimidin-6-one
• CAS: 1431331-23-5
• 化学式: C₁₀H₈FN₃O
• 分子量: 205.191
• InChiKey: VCDWELIOYPRYBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-fluoro-4-methyl-2-pyridin-2-yl-1H-pyrimidin-6-one 在 potassium carbonate 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 5-fluoro-6-methyl-N-(2-phenylethyl)-2-pyridin-2-ylpyrimidin-4-amine
  参考文献：
  名称：

  Pyridinylpyrimidines selectively inhibit human methionine aminopeptidase-1

  摘要：

  Cellular protein synthesis is initiated with methionine in eukaryotes with few exceptions. Methionine aminopeptidases (MetAPs) which catalyze the process of N-terminal methionine excision are essential for all organisms. In mammals, type 2 MetAP (MetAP2) is known to be important for angiogenesis, while type 1 MetAP (MetAP1) has been shown to play a pivotal role in cell proliferation. Our previous high-throughput screening of a commercial compound library uncovered a novel class of inhibitors for both human MetAP1 (HsMetAP1) and human MetAP2 (HsMetAP2). This class of inhibitors contains a pyridinylpyrimidine core. To understand the structure-activity relationship (SAR) and to search for analogues of 2 with greater potency and higher HsMetAP1-selectivity, a total of 58 analogues were acquired through either commercial source or by in-house synthesis and their inhibitory activities against HsMetAP1 and HsMetAP2 were determined. Through this systematic medicinal chemistry analysis, we have identified (1) 5-chloro-6-methyl-2-pyridin-2-ylpyrimidine as the minimum element for the inhibition of HsMetAP1; (2) 5'-chloro as the favored substituent on the pyridine ring for the enhanced potency against HsMetAP1; and (3) long C4 side chains as the essentials for higher HsMetAP1-selectivity. At the end of our SAR campaign, 25b, 25c, 26d and 30a-30c are among the most selective and potent inhibitors of purified HsMetAP1 reported to date. In addition, we also performed crystallographic analysis of one representative inhibitor (26d) in complex with N-terminally truncated HsMetAP1. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.023
• 作为产物：
  描述：

  2-氰基吡啶 在 甲醇 、 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 5-fluoro-4-methyl-2-pyridin-2-yl-1H-pyrimidin-6-one
  参考文献：
  名称：

  Pyridinylpyrimidines selectively inhibit human methionine aminopeptidase-1

  摘要：

  Cellular protein synthesis is initiated with methionine in eukaryotes with few exceptions. Methionine aminopeptidases (MetAPs) which catalyze the process of N-terminal methionine excision are essential for all organisms. In mammals, type 2 MetAP (MetAP2) is known to be important for angiogenesis, while type 1 MetAP (MetAP1) has been shown to play a pivotal role in cell proliferation. Our previous high-throughput screening of a commercial compound library uncovered a novel class of inhibitors for both human MetAP1 (HsMetAP1) and human MetAP2 (HsMetAP2). This class of inhibitors contains a pyridinylpyrimidine core. To understand the structure-activity relationship (SAR) and to search for analogues of 2 with greater potency and higher HsMetAP1-selectivity, a total of 58 analogues were acquired through either commercial source or by in-house synthesis and their inhibitory activities against HsMetAP1 and HsMetAP2 were determined. Through this systematic medicinal chemistry analysis, we have identified (1) 5-chloro-6-methyl-2-pyridin-2-ylpyrimidine as the minimum element for the inhibition of HsMetAP1; (2) 5'-chloro as the favored substituent on the pyridine ring for the enhanced potency against HsMetAP1; and (3) long C4 side chains as the essentials for higher HsMetAP1-selectivity. At the end of our SAR campaign, 25b, 25c, 26d and 30a-30c are among the most selective and potent inhibitors of purified HsMetAP1 reported to date. In addition, we also performed crystallographic analysis of one representative inhibitor (26d) in complex with N-terminally truncated HsMetAP1. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.023

文献信息

• Screening and Synthesis of Tetrazole Derivatives that Inhibit the Growth of <i>Cryptococcus</i> Species
  作者：Nana Nakada、Taiga Miyazaki、Satoshi Mizuta、Tatsuro Hirayama、Seiko Nakamichi、Kohsuke Takeda、Hiroshi Mukae、Shigeru Kohno、Yoshimasa Tanaka

  DOI：10.1002/cmdc.202300157

  日期：2023.9.15

  The compounds 8-fluoro-7-methyl-5-(pyridin-2-yl)tetrazolo[1,5-c]pyrimidine and 5-(pyridin-2-yl)-8,9-dihydro-7H-cyclopenta[e]tetrazolo[1,5-c]pyrimidine belong to a novel class of antifungals. Both compounds with tetrazole backbone exhibit inhibitory activity that is equivalent or superior to those of conventional drugs on a weight-per-volume basis, with IC50 equalling 0.05 μM (0.012 μg mL−1) against

  化合物8-氟-7-甲基-5-(吡啶-2-基)四唑并[1,5-c]嘧啶和5-(吡啶-2-基)-8,9-二氢-7H-环戊基[e ]四唑并[1,5-c]嘧啶属于一类新型抗真菌药。两种具有四唑骨架的化合物均表现出与传统药物相同或优于传统药物的抑制活性（按重量/体积计算），对每种隐球菌属物种的 IC 50等于 0.05 μM (0.012 μg mL -1 ) 。因此，含四唑主链的化合物可能是具有独特抗隐球菌病机制的新型抗真菌药物。抗真菌药物念珠菌隐球菌高通量筛选四唑
• Pyridinylpyrimidines selectively inhibit human methionine aminopeptidase-1
  作者：Pengtao Zhang、Xinye Yang、Feiran Zhang、Sandra B. Gabelli、Renxiao Wang、Yihua Zhang、Shridhar Bhat、Xiaochun Chen、Manuel Furlani、L. Mario Amzel、Jun O. Liu、Dawei Ma

  DOI：10.1016/j.bmc.2013.02.023

  日期：2013.5

  Cellular protein synthesis is initiated with methionine in eukaryotes with few exceptions. Methionine aminopeptidases (MetAPs) which catalyze the process of N-terminal methionine excision are essential for all organisms. In mammals, type 2 MetAP (MetAP2) is known to be important for angiogenesis, while type 1 MetAP (MetAP1) has been shown to play a pivotal role in cell proliferation. Our previous high-throughput screening of a commercial compound library uncovered a novel class of inhibitors for both human MetAP1 (HsMetAP1) and human MetAP2 (HsMetAP2). This class of inhibitors contains a pyridinylpyrimidine core. To understand the structure-activity relationship (SAR) and to search for analogues of 2 with greater potency and higher HsMetAP1-selectivity, a total of 58 analogues were acquired through either commercial source or by in-house synthesis and their inhibitory activities against HsMetAP1 and HsMetAP2 were determined. Through this systematic medicinal chemistry analysis, we have identified (1) 5-chloro-6-methyl-2-pyridin-2-ylpyrimidine as the minimum element for the inhibition of HsMetAP1; (2) 5'-chloro as the favored substituent on the pyridine ring for the enhanced potency against HsMetAP1; and (3) long C4 side chains as the essentials for higher HsMetAP1-selectivity. At the end of our SAR campaign, 25b, 25c, 26d and 30a-30c are among the most selective and potent inhibitors of purified HsMetAP1 reported to date. In addition, we also performed crystallographic analysis of one representative inhibitor (26d) in complex with N-terminally truncated HsMetAP1. (C) 2013 Elsevier Ltd. All rights reserved.