2,5-diamino-4-benzylamino-6-chloropyrimidine | 186416-92-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,5-diamino-4-benzylamino-6-chloropyrimidine
• 英文别名: N~4~-benzyl-6-chloropyrimidine-2,4,5-triamine；4-N-benzyl-6-chloropyrimidine-2,4,5-triamine
• CAS: 186416-92-2
• 化学式: C₁₁H₁₂ClN₅
• 分子量: 249.703
• InChiKey: GWPZTAIOHLGMCI-UHFFFAOYSA-N

物化性质

• 沸点：
  509.3±60.0 °C(Predicted)
• 密度：
  1.447±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  89.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,5-diamino-4-benzylamino-6-chloropyrimidine 在 溶剂黄146 、 sodium nitrite 作用下， 反应 3.0h， 以87%的产率得到3-Benzyl-7-chlorotriazolo[4,5-d]pyrimidin-5-amine
  参考文献：
  名称：

  区域选择性合成9-取代的8-氮杂鸟嘌呤（5-氨基-3-取代的3,6-二氢-7 H -1,2,3-三唑并[4,5- d ]嘧啶-7-一）

  摘要：

  通过修改先前描述的由咪唑合成9-取代鸟嘌呤的方法，我们开发了9-取代-8-氮杂鸟嘌呤（5-氨基-3-取代-3,6-二氢-来自三唑的7 H -1,2,3-三唑并[4,5- d ]嘧啶-7-one）高产率。该方法似乎适合引入各种取代基，包括糖，碳环，无环和碳环链。

  DOI：

  10.1002/jhet.5570330609
• 作为产物：
  描述：

  2-amino-4-benzylamino-5-(p-chlorophenylazo)-6-chloropyrimidine 在 溶剂黄146 、 锌 作用下， 以 乙醇 、 水 为溶剂， 生成 2,5-diamino-4-benzylamino-6-chloropyrimidine
  参考文献：
  名称：

  小分子免疫刺激剂。7,8-二取代鸟苷和结构相关化合物的合成及活性。

  摘要：

  设计并制备了一系列的7,8-二取代鸟苷衍生物，作为体液免疫反应的潜在B细胞选择性激活剂。评估了这些化合物充当B细胞有丝分裂原和增强B细胞对绵羊红细胞（SRBC）攻击（佐剂）的抗体反应的能力。此外，在鼠体外细胞试验中测试了它们刺激自然杀伤（NK）细胞反应的能力。当静脉内，皮下或口服给药时，某些化合物表现出体内活性。发现在7-烷基-8-氧代鸟苷的7-位上具有中等长度的烷基链（2-4个碳，5-7）的类似物特别有效。在该7位上带有羟烷基，氨基烷基或取代的氨基烷基取代基的化合物是弱活性的。然而，苄基，包括被杂原子取代的那些（例如，对硝基苄基，14）是有活性的。鸟苷环的C-8上的氧，硫代和硒代基团均具有很强的活性，而其他较大的取代基则没有（例如N = CN）。在该系列中，核糖环上2'-羟基的立体化学转化，使阿拉伯糖类似物70的活性降低。然而，通过（64）或没有（73）的3'羟基的去除2'-羟基导致了优

  DOI：

  10.1021/jm00047a014

文献信息

• Design, Synthesis, and Bioevaluation of 2-Aminopteridin-7(8<i>H</i>)-one Derivatives as Novel Potent Adenosine A_2A Receptor Antagonists for Cancer Immunotherapy
  作者：Fazhi Yu、Chenyu Zhu、Shuyin Ze、Haojie Wang、Xinyu Yang、Mingyao Liu、Qiong Xie、Weiqiang Lu、Yonghui Wang

  DOI：10.1021/acs.jmedchem.1c02199

  日期：2022.3.10

  In recent years, the adenosine A2A receptor (A2AR) has shown exciting progress in the development of immunotherapies for the treatment of cancer. Herein, a 2-amino-7,9-dihydro-8H-purin-8-one compound (1) was identified as an A2AR antagonist hit through in-house library screening. Extensive structure–activity relationship (SAR) studies led to the discovery of 2-aminopteridin-7(8H)-one derivatives, which

  近年来，腺苷A 2A受体(A 2A R) 在用于治疗癌症的免疫疗法的开发中显示出令人兴奋的进展。在此，一种2-氨基-7,9-二氢-8H-嘌呤-8-酮化合物( 1 )通过内部文库筛选被鉴定为A 2AR拮抗剂。广泛的构效关系 (SAR) 研究导致发现了 2-氨基蝶啶-7(8 H )-one 衍生物，该衍生物在 cAMP 测定中显示出对 A 2A R 的高效力。化合物57在 5'- N处对 A 2A R的 IC 50值为 8.3 ± 0.4 nM-乙基羧酰胺腺苷 (NECA) 水平为 40 nM。即使在 1 μM 的较高 NECA 浓度下， 57的拮抗作用也能持续，这模拟了肿瘤微环境 (TME) 中的腺苷水平。重要的是，57在 IL-2 产生测定和癌细胞杀伤模型中均增强了 T 细胞活化，从而证明了其作为在癌症免疫治疗中开发新型 A 2AR拮抗剂的先导潜力。
• Triazolopyrimidines and related analogs as HSP90-inhibitors
  申请人：Kasibhatla Rao Srinivas

  公开号：US20050113339A1

  公开（公告）日：2005-05-26

  Triazolopyrimidines and related compounds are described and demonstrated or predicted to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents in the treatment and prevention of various HSP90 mediated disorders, e.g., proliferative disorders. Method of synthesis and use of such compounds are also described and claimed.

  描述了三唑并嘧啶和相关化合物，并证明或预测其在治疗和预防各种HSP90介导的疾病，例如增殖性疾病中作为热休克蛋白90（HSP90）抑制剂的效用。还描述和声明了这些化合物的合成方法和使用方法。
• Deazapurine derivatives as HSP90-Inhibitors
  申请人：Conforma Therapeutics Corporation

  公开号：EP2145888A1

  公开（公告）日：2010-01-20

  Heterobicyclic compounds of formula I are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agent. Method of synthesis and use of such compounds are also described.

  描述并证明了式 I 的杂双环化合物作为热休克蛋白 90（HSP90）抑制剂的实用性。还描述了合成和使用此类化合物的方法。
• Synthesis and in vitro evaluation of novel 2,6,9-trisubstituted purines acting as cyclin-dependent kinase inhibitors
  作者：Michel Legraverend、Odile Ludwig、Emile Bisagni、Sophie Leclerc、Laurent Meijer、Nicole Giocanti、Ramin Sadri、Vincent Favaudon

  DOI：10.1016/s0968-0896(99)00064-4

  日期：1999.7

  Novel C-2, C-6, N-9 trisubstituted purines derived from the olomoucine/roscovitine lead structure were synthesized and evaluated for their ability to inhibit starfish oocyte CDK1/cyclin B, neuronal CDK5/p35 and erk1 kinases in purified extracts. Structure-activity relationship studies showed that increased steric bulk at N-9 reduces the inhibitory potential whereas substitution of the aminoethanol C-2 side chain by various groups of different size (methyl, propyl, butyl, phenyl, benzyl) only slightly decreases the activity when compared to (R)-roscovitine. Optimal inhibitory activity against CDK5, CDK1 and CDK2, with IC50 values of 0.16, 0.45 and 0.65 mu M, respectively, was obtained with compound 21 containing a (2R)-pyrrolidin-2-yl-methanol substituent at the C-2 and a 3-iodobenzylamino group at the C-6 of the purine. Compound 21 proved cytotoxic against human tumor HeLa cells (LD50 = 6.7 mu M versus 42.7 mu M for olomoucine, 24-h contact). Furthermore, unlike olomoucine, compound 21 was effective upon short exposure (LD50 = 25.3 mu M, 2-h contact). The available data suggest that the affinity for CDKs and the cytotoxic potential of the drugs are inter-related. However, no straightforward cell cycle phase specificity of the cytotoxic response to 21 was observed in synchronized HeLa cells. With the noticeable exception of pronounced lengthening of the S-phase transit by 21 applied during early-S in synchronized HeLa cells, and in striking contrast with earlier reports on studies using plant or echinoderm cells, olomoucine and compound 21 were unable to reversibly arrest cell cycle progression in asynchronous growing HeLa cells. Some irreversible block in G1 and G2 phase occurred at high olomoucine concentration, correlated with induced cell death. Moreover, chronic exposure to lethal doses of compound 21 resulted in massive nuclear fragmentation, evocative of mitotic catastrophe with minor amounts of apoptosis only. It was also found that olomoucine and compound 21 reversibly block the intracellular uptake of nucleosides with high efficiency. (C) 1999 Elsevier Science Ltd. All rights reserved.
• US7129244B2
  申请人：——

  公开号：US7129244B2

  公开（公告）日：2006-10-31