5-(苄氧基甲基)-1H-吡唑-3-胺 | 1185908-13-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-(苄氧基甲基)-1H-吡唑-3-胺
• 英文名称: 5-[(phenylmethoxy)methyl]-1H-pyrazol-3-amine
• 英文别名: 3-(benzyloxymethyl)-1H-pyrazol-5-amine；5-benzyloxymethyl-2H-pyrazol-3-ylamine；5-((Benzyloxy)methyl)-1H-pyrazol-3-amine；5-(phenylmethoxymethyl)-1H-pyrazol-3-amine
• CAS: 1185908-13-7；393590-62-0
• 化学式: C₁₁H₁₃N₃O
• 分子量: 203.244
• InChiKey: YIBUHJHRURIGRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  63.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(苄氧基甲基)-1H-吡唑-3-胺 在 4-二甲氨基吡啶 、 sodium hydride 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 tert-butyl 5-[(benzyloxy)methyl]-3-({[(5-oxo-2,3,5,9b-tetrahydro-1H-pyrrolo[2,1-α]isoindol-9-yl)amino]carbonyl}amino)-1H-pyrazole-1-carboxylate
  参考文献：
  名称：

  A Novel Approach for the Development of Selective Cdk4 Inhibitors:  Library Design Based on Locations of Cdk4 Specific Amino Acid Residues

  摘要：

  Identification of a selective inhibitor for a particular protein kinase without inhibition of other kinases is critical for use as a biological tool or drug. However, this is very difficult because there are hundreds of homologous kinases and their kinase domains including the ATP binding pocket have a common folding pattern. To address this issue, we applied the following structure-based approach for designing selective Cdk4 inhibitors: (1) identification of specifically altered amino acid residues around the ATP binding pocket in Cdk4 by comparison of 390 representative kinases, (2) prediction of appropriate positions to introduce substituents in lead compounds based on the locations of the altered amino acid residues and the binding modes of lead compounds, and (3) library design to interact with the altered amino acid residues supported by de novo design programs. Accordingly, Asp99, Thr102, and Gln98 of Cdk4, which are located in the p16 binding region, were selected as first target residues for specific interactions with Cdk4. Subsequently, the 5-position of the pyrazole ring in the pyrazol-3-ylurea class of lead compound (2a) was predicted to be a suitable position to introduce substituents. We then designed a chemical library of pyrazol-3-ylurea substituted with alkylaminomethyl groups based on the output structures of de novo design programs. Thus we identified a highly selective and potent Cdk4 inhibitor, 15b, substituted with a 5-chloroindan-2-ylaminomethyl group. Compound 15b showed higher selectivity on Cdk4 over those on not only Cdk1/2 (780-fold/190-fold) but also many other kinases (> 430-fold) that have been tested thus far. The structural basis for Cdk4 selective inhibition by 15b was analyzed by combining molecular modeling and the X-ray analysis of the Cdk4 mimic Cdk2-inhibitor complex. The results suggest that the hydrogen bond with the carboxyl group of Asp99 and hydrophobic van der Waals contact with the side chains of Thr102 and Gln98 are important. Compound 15b was found to cause cell cycle arrest of the Rb(+) cancer cell line in the G(1) phase, indicating that it is a good biological tool.

  DOI：

  10.1021/jm010326y
• 作为产物：
  描述：

  苄氧基乙酸乙酯 在 正丁基锂 、 hydrazine hydrate 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 为溶剂， 反应 19.0h， 生成 5-(苄氧基甲基)-1H-吡唑-3-胺
  参考文献：
  名称：

  吡唑并[1,5-a]嘧啶衍生物作为新型选择性PI3Kδ抑制剂系列的设计、合成和开发：第一部分-吲哚衍生物

  摘要：

  磷酸肌醇 3-激酶δ (PI3K δ ) 是 I 类 PI3K 家族的成员，是调节免疫细胞分化、增殖、迁移和存活的重要信号生物分子。这种蛋白质的过度活性会导致许多人类疾病的细胞功能障碍，例如炎症和自身免疫性疾病，包括哮喘或慢性阻塞性肺病 (COPD)。在这项工作中，我们设计并合成了一个新的基于吲哚-4-基-吡唑并[1,5- a ]嘧啶的小分子抑制剂库，IC 50值在低纳摩尔范围内，对 PI3K δ异构体具有高选择性. CPL302253 ( 54) 是所获得的所有结构中最有效的化合物，IC 50 = 2.8 nM，是未来临床开发用于预防哮喘的吸入药物的潜在候选药物。

  DOI：

  10.3390/ph15080949

文献信息

• [EN] PYRAZOLE [3, 4-B] PYRIDINE RAF INHIBITORS<br/>[FR] INHIBITEURS DE RAF DE PYRAZOLE[3,4-B]PYRIDINE
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2009111279A1

  公开（公告）日：2009-09-11

  Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  公式I的化合物对于抑制Raf激酶很有用。本文揭示了利用公式I的化合物及其立体异构体、互变异构体、前药和药学上可接受的盐，在哺乳动物细胞中进行体外、体内和体内诊断、预防或治疗此类疾病或相关病理条件的方法。
• [EN] 7-(MORPHOLIN-4-YL)PYRAZOLE[1,5-A]PYRIMIDINE DERIVATIVES WHICH ARE USEFUL FOR THE TREATMENT OF IMMUNE OR INFLAMMATORY DISEASES OR CANCER<br/>[FR] DÉRIVÉS 7-(MORPHOLIN-4-YL)PYRAZOLE[1,5-A]PYRIMIDINE QUI SONT UTILES POUR LE TRAITEMENT DE MALADIES IMMUNITAIRES OU INFLAMMATOIRES OU DU CANCER
  申请人：CELON PHARMA SA

  公开号：WO2016157091A1

  公开（公告）日：2016-10-06

  A compound of the general formula (I) wherein Y represents -CH2- or >C=0; R1 is selected from the group consisting of A1, A2 and A3; R2 represents dioxothiomorpholino moiety B1, piperazinyl moiety B2, azetidinyl moiety B3, or piperidinyl moiety B4; R3 is selected from the group consisting of H, halogen, and C1 -C4 alkyl; R4 is selected from the group consisting of C1 -C4 alkyl, C3-C4- cycloalkyl, C1 -C4 alkyl substituted with C1 -C4 alkoxy, and CHF2, and their pharmaceutically acceptable salts. Pharmaceutical compositions comprising said compounds and their use in the treatment of diseases of immune system, inflammatory diseases and cancer.

  通用式（I）的化合物，其中Y代表-CH2-或>C=0；R1从A1、A2和A3组成的群体中选择；R2代表二氧硫吗啉基团B1、哌嗪基团B2、氮杂环丁基团B3或哌啶基团B4；R3从H、卤素和C1-C4烷基组成的群体中选择；R4从C1-C4烷基、C3-C4环烷基、C1-C4烷基取代的C1-C4烷氧基和CHF2组成的群体中选择，以及它们的药学上可接受的盐。包括所述化合物的药物组合物及其在治疗免疫系统疾病、炎症性疾病和癌症中的用途。
• [EN] OGA INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS D'OGA
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2019243531A1

  公开（公告）日：2019-12-26

  The present invention relates to O-GIcNAc hydrolase (OGA) inhibitors of formula (I). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C90RF72 mutations. RB is a radical selected from the group consisting of (b-1) to (b-4).

  本发明涉及式(I)的O-GIcNAc水解酶（OGA）抑制剂。该发明还涉及包含这类化合物的药物组合物，制备这类化合物和组合物的方法，以及利用这类化合物和组合物预防和治疗OGA抑制对益处的疾病，如特别是tau病变性疾病，如阿尔茨海默病或进行性核上性麻痹症；以及伴有tau病理的神经退行性疾病，特别是由C90RF72突变引起的肌萎缩性侧索硬化或前颞叶痴呆症。RB是从（b-1）到（b-4）组成的基团中选取的基团。
• [EN] HETEROCYCLIC COMPOUNDS AS INHIBITORS OF CXCR2<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES COMME INHIBITEURS DE CXCR2
  申请人：NOVARTIS AG

  公开号：WO2009106539A1

  公开（公告）日：2009-09-03

  The present invention relates to compounds of formula (I) wherein R1, R2, X, Y and Z are as defined in the specification.

  本发明涉及公式（I）中R1、R2、X、Y和Z所定义的化合物。
• PYRAZOLE [3, 4-B] PYRIDINE RAF INHIBITORS
  申请人：Ahrendt Kateri A.

  公开号：US20110092479A1

  公开（公告）日：2011-04-21

  Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  公式I的化合物对于抑制Raf激酶非常有用。本文揭示了使用公式I及其立体异构体、互变异构体、前药和药学上可接受的盐，用于哺乳动物细胞中的体外、原位和体内诊断、预防或治疗相关病理状况的方法。