5-Amino-1-tert-butyl-3-naphthalen-2-yl-1H-pyrazole-4-carbonitrile | 198968-26-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-Amino-1-tert-butyl-3-naphthalen-2-yl-1H-pyrazole-4-carbonitrile
• 英文别名: 5-Amino-1-(1,1-dimethylethyl)-3-(1-naphthalenyl)-1H-pyrazole-4-carbonitrile；5-amino-1-tert-butyl-3-naphthalen-2-ylpyrazole-4-carbonitrile
• CAS: 198968-26-2
• 化学式: C₁₈H₁₈N₄
• 分子量: 290.368
• InChiKey: DZSWVSBKEMEABO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  67.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-Amino-1-tert-butyl-3-naphthalen-2-yl-1H-pyrazole-4-carbonitrile 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 0.33h， 生成 5-amino-1-tert-butyl-3-(naphthalen-2-yl)-1H-pyrazole-4-carboxamide
  参考文献：
  名称：

  Potent and Selective Inhibitors of CDPK1 from T. gondii and C. parvum Based on a 5-Aminopyrazole-4-carboxamide Scaffold

  摘要：

  5-Aminopyrazole-4-carboxamide was used as an alternative scaffold to substitute for the pyrazolopyrimidine of a known "bumped kinase inhibitor" to create selective inhibitors of calcium-dependent protein kinase-1 from both Toxoplasma gondii and Cryptosporidium parvum. Compounds with low nanomolar inhibitory potencies against the target enzymes were obtained. The most selective inhibitors also exhibited submicromolar activities in T. gondii cell proliferation assays and were shown to be non-toxic to mammalian cells.

  DOI：

  10.1021/ml400315s
• 作为产物：
  描述：

  2-萘甲酰氯 在 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 5-Amino-1-tert-butyl-3-naphthalen-2-yl-1H-pyrazole-4-carbonitrile
  参考文献：
  名称：

  1,3-二取代-4-氨基吡唑并[3，4-d]嘧啶，一类新型的磷脂酶D抑制剂

  摘要：

  磷脂酶D酶裂解脂质底物以产生磷脂酸，磷脂酸是许多必需细胞分子的重要前体。磷脂酶D是调节癌细胞侵袭性的靶标。这项研究报告了基于1,3-二取代-4-氨基-吡唑并嘧啶核心结构的新型磷脂酶D抑制剂的合成。这些分子被合成并用于为纯化的细菌磷脂酶d的抑制，这是高度同源的人的PLD执行初步筛选1。最初用细菌磷脂酶D酶进行测试，然后用重组人PLD 1和PLD 2酶确认，此处显示的分子表现出对磷脂酶D活性的抑制作用（IC 50）在低纳摩尔至低微摩尔范围内，同时具有单体底物diC 4 PC和磷脂囊泡和胶束。数据强烈表明这些抑制分子直接阻断了酶/囊泡底物的结合。初步活性研究使用重组人磷脂酶Ds在体内细胞测定中测量了转磷脂酰化和头部裂解，表明在生理环境中这些有效的抑制性新分子在中低纳摩尔范围内具有抑制作用。

  DOI：

  10.1111/cbdd.12319

文献信息

• A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells
  作者：Gang Zhang、Shan Li、Feng Wang、Amanda C. Jones、Alexander F.G. Goldberg、Benjamin Lin、Scott Virgil、Brian M. Stoltz、Raymond J. Deshaies、Tsui-Fen Chou

  DOI：10.1016/j.ejmech.2020.113148

  日期：2021.3

  study the structure-activity relationship. In addition, we used p97 structures to design and synthesize analogues of pyrazolo[3,4-d]pyrimidine (PP). We incorporated electrophiles into a PP-like compound 17 (4-amino-1-tert-butyl-3-phenyl pyrazolo[3,4-d]pyrimidine) to generate eight compounds. A selective compound 18 (N-(1-(tert-butyl)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)acrylamide, PPA) exhibited

  p97 的小分子抑制剂是研究 p97 功能的有用工具。人 p97 是一种重要的 AAA ATP 酶，因为它具有多种细胞功能，并且在介导与肿瘤发生和病毒感染有关的蛋白质转换方面具有重要意义。从先前的高通量筛选研究中鉴定出的多种 p97 抑制剂是针对 D2 ATP 结合域中的 Cys522 的硫醇反应性化合物。因此，这些发现表明了开发共价 p97 抑制剂的潜在策略。我们首先使用纯化的 p97 来检测几种已知的共价激酶抑制剂，以确定它们是否可以抑制 ATP 酶活性。我们使用可以区分 p97 依赖性和独立降解的双报告细胞评估了它们的选择性。我们选择了β-硝基苯乙烯支架来进一步研究构效关系。此外，d ]嘧啶（PP）。我们将亲电子试剂加入到类 PP 化合物17（4-氨基-1-叔丁基-3-苯基吡唑并[3,4- d ]嘧啶）中，生成八种化合物。选择性化合物18 ( N -(1-( tert -butyl )-3-phenyl-1
• Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii
  作者：Sebastian Lourido、Chao Zhang、Michael S. Lopez、Keliang Tang、Jennifer Barks、Qiuling Wang、Scott A. Wildman、Kevan M. Shokat、L. David Sibley

  DOI：10.1021/jm4001314

  日期：2013.4.11

  Toxoplasma gondii is sensitive to bulky pyrazolo [3,4-d] pyrimidine (PP) inhibitors due to the presence of a Gly gatekeeper in the essential calcium dependent protein kinase 1 (CDPK1). Here we synthesized a number of new derivatives of 3-methyl-benzyl-PP (3-MB-PP, or 1). The potency of PP analogues in inhibiting CDPK1 enzyme activity in vitro (low nM IC50 values) and blocking parasite growth in host cell monolayers in vivo (low mu M EC50 values) were highly correlated and occurred in a CDPK1-specific manner. Chemical modification of the PP scaffold to increase half-life in the presence of microsomes in vitro led to identification of compounds with enhanced stability while retaining activity. Several of these more potent compounds were able to prevent lethal infection with T. gondii in the mouse model. Collectively, the strategies outlined here provide a route for development of more effective compounds for treatment of toxoplasmosis and perhaps related parasitic diseases.
• Generation of Monospecific Nanomolar Tyrosine Kinase Inhibitors via a Chemical Genetic Approach
  作者：Anthony C. Bishop、Chi-yun Kung、Kavita Shah、Laurie Witucki、Kevan M. Shokat、Yi Liu

  DOI：10.1021/ja983267v

  日期：1999.2.1

  Selective protein kinase inhibitors are highly sought after as tools for studying cellular signal transduction cascades, yet few have been discovered due to the highly conserved fold of kinase catalytic domains. Through a combination of small molecule synthesis and protein mutagenesis, a highly potent (IC50 = 1.5 nM) and uniquely specific inhibitor (4-amino-1-tert-butyl-3-(1'-naphthyl)pyrazolo[3,4-d]pyrimidine) of a rationally engineered v-Src tyrosine kinase (Ile338Gly v-Src) has been identified. Both the potency and specificity of this compound surpass those of any known Src family tyrosine kinase inhibitors. The molecule strongly inhibits the engineered v-Src in whole cells but does not inhibit tyrosine phosphorylation in cells that express only wild-type tyrosine kinases. In addition, the inhibitor selectively disrupts transformation in cells that express the target v-Src. The structural degeneracy of kinase active sites should allow the same complementary inhibitor/protein design strategy to be widely applicable across this entire enzyme superfamily.
• 5-AMINOPYRAZOLES USEFUL AS SELECTIVE INHIBITORS OF THE PROTEIN TYROSINE KINASE P56ICK
  申请人：CELLTECH THERAPEUTICS LIMITED

  公开号：EP0906286A1

  公开（公告）日：1999-04-07
• US5922741A
  申请人：——

  公开号：US5922741A

  公开（公告）日：1999-07-13