1-甲基-3-氨基-4-氰基吡唑 | 21230-50-2

• 物质功能分类: 有机原料 - 氨基化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 亚胺内酰胺
• 中文名称: 1-甲基-3-氨基-4-氰基吡唑
• 英文名称: 3-amino-1-methyl-1H-pyrazole-4-carbonitrile
• 英文别名: 3-amino-1-methylpyrazole-4-carbonitrile；3-amino-1-methylpyrazol-4-carbonitrile；1-Methyl-3-amino-4-cyanopyrazole
• CAS: 21230-50-2
• 化学式: C₅H₆N₄
• mdl: MFCD11040163
• 分子量: 122.129
• InChiKey: FBQOIRKIQMQJNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  67.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933199090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  1-甲基-3-氨基-4-氰基吡唑 在 N-甲基吡咯烷酮 、 盐酸 、 对甲苯磺酸 作用下， 以 二苯醚 、 乙二醇甲醚 、 水 为溶剂， 反应 70.0h， 生成 N’’-[2-(2-furyl)-8-methyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl]-N,N’-bis(4-bromophenyl)guanidine
  参考文献：
  名称：

  One-Pot Reaction To Obtain N,N′-Disubstituted Guanidines of Pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine Scaffold as Human A₃ Adenosine Receptor Antagonists

  摘要：

  In this paper we describe an extension SAR study of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine nucleus as A(3)AR antagonist. Our initial aim was to replace the phenylcarbamoyl moiety at the 5 position of PTP nucleus with a thiourea functionality to evaluate the contribution of new structural modification against the A(3)AR. The synthesized 12-25 were not characterized by the predicted side chain but by a 1,3-disubstituted guanidine and are shown to be interesting A(3)AR antagonists.

  DOI：

  10.1021/acs.jmedchem.5b00551
• 作为产物：
  描述：

  {[(2Z)-2-benzylidene-1-methylhydrazino]methylene}-malononitrile 在 盐酸 作用下， 以 水 为溶剂， 生成 1-甲基-3-氨基-4-氰基吡唑
  参考文献：
  名称：

  Does the combination of optimal substitutions at the C2-, N5- and N8-positions of the pyrazolo-triazolo-pyrimidine scaffold guarantee selective modulation of the human A3 adenosine receptors?

  摘要：

  In an attempt to study the optimal combination of a phenyl ring at the C-2-position and different substituents at the N-5- and N-8-positions towards the selective modulation of human A(3) adenosine receptors (hA(3)AR), we synthesized a new series of 2-para-(un)substituted-phenyl-pyrazolo-triazolo-pyrimidines bearing either a methyl or phenylethyl at N-8 and chains of variable length at N-5. Through biological evaluation, it was found that the majority of the compounds had good affinities towards the hA(3)AR in the low nanomolar range. Compound 16 possessed the best hA(3)AR affinity and selectivity profile (K(i)hA(3) = 1.33 nM; hA(1)/hA(3) = 4880; hA(2A)/hA(3) = 1100) in the present series of2-(substituted)phenylpyrazolo-triazolo-pyrimidine derivatives. In addition to pharmacological characterization, a molecular modeling investigation on these compounds further elucidated the effect of different substituents at the pyrazolo-triazolo-pyrimidine scaffold on affinity and selectivity to hA3AR. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.026

文献信息

• [EN] AZOLOPYRIDINE AND AZOLOPYRIMIDINE COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS D'AZOLOPYRIDINE ET D'AZOLOPYRIMIDINE ET MÉTHODES D'UTILISATION ASSOCIÉES
  申请人：AMBIT BIOSCIENCES CORP

  公开号：WO2012030924A1

  公开（公告）日：2012-03-08

  Provided herein are azolopyridine and azolopyrimidine compounds for treatment of JAK kinase mediated diseases, including JAK2 kinase-, JAK3 kinase- or TYK2 kinase-mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.

  本文提供了用于治疗JAK激酶介导疾病的咪唑吡啶和咪唑吡啶化合物，包括JAK2激酶、JAK3激酶或TYK2激酶介导的疾病。还提供了包含这些化合物的药物组合物以及使用这些化合物和组合物的方法。
• [EN] RECEPTOR TYROSINE KINASE INHIBITORS FOR TREATMENT OF PROTEIN KINASE MODULATION-RESPONSIVE DISEASE OR DISORDER<br/>[FR] INHIBITEURS DU RÉCEPTEUR DE LA TYROSINE KINASE POUR LE TRAITEMENT DE MALADIE OU DE TROUBLE SENSIBLE À LA MODULATION DE LA PROTÉINE KINASE
  申请人：US HEALTH

  公开号：WO2021050900A1

  公开（公告）日：2021-03-18

  Ephrin type receptor tyrosine kinase inhibitors, also known as Eph tyrosine kinase receptor inhibitors, for treating cancer, an inflammatory disease, an autoimmune disease, or a degenerative disease characterized at least in part by the abnormal activity or expression of the Eph receptor tyrosine kinase. The inhibitors are particularly useful for treating colorectal cancer.

  Ephrin类型受体酪氨酸激酶抑制剂，也被称为Eph酪氨酸激酶受体抑制剂，用于治疗癌症、炎症性疾病、自身免疫疾病或部分特征为Eph受体酪氨酸激酶异常活性或表达的退行性疾病。这些抑制剂特别适用于治疗结直肠癌。
• N-SUBSTITUTED-DIOXOCYCLOBUTENYLAMINO-3-HYDROXY-PICOLINAMIDES USEFUL AS CCR6 INHIBITORS
  申请人：Pfizer Inc.

  公开号：US20200095239A1

  公开（公告）日：2020-03-26

  The present invention relates to N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamide compounds of Formulae (IA and 1B) or a pharmaceutically acceptable salt or hydrate thereof, that inhibit CC chemokine receptor 6 (CCR6), pharmaceutical compositions containing these compounds, and the use of these compounds for treating or preventing diseases, conditions, or disorders ameliorated by inhibition of CCR6.

  本发明涉及式(IA和1B)所示的N-取代-二氧环丁烯基氨基-3-羟基-吡咯烷酰胺化合物或其药用可接受盐或水合物，这些化合物抑制CC趋化因子受体6 (CCR6)，包含这些化合物的药物组合物，以及使用这些化合物来治疗或预防通过抑制CCR6而改善的疾病、状况或失调。
• [EN] 2,4,6,7-TETRAHYDRO-PYRAZOLO[4,3-D]PYRIMIDIN-5-ONE DERIVATIVES AND RELATED COMPOUNDS AS C5A RECEPTOR MODULATORS FOR TREATING VASCULITIS AND INFLAMMATORY DISEASES<br/>[FR] DÉRIVÉS DE 2,4,6,7-TÉTRAHYDRO-PYRAZOLO[4,3-D]PYRIMIDIN-5-ONE ET COMPOSÉS APPARENTÉS EN TANT QUE MODULATEURS DU RÉCEPTEUR C5A POUR LE TRAITEMENT DE LA VASCULARITE ET DE MALADIES INFLAMMATOIRES
  申请人：IDORSIA PHARMACEUTICALS LTD

  公开号：WO2019137927A1

  公开（公告）日：2019-07-18

  The present invention relates to derivatives of formula (I) wherein Ring A, X, Y, Z, RA, R1, R2, R3 and R4 are The present invention discloses derivatives of formula (I), wherein Ring A, X, Y, Z, RA, R1, R2, R3 and R4 are as described in the description, and in particular e.g. 2,4,6,7-tetrahydro-pyrazolo[4,3- d]pyrimidin-5-one derivatives and related compounds, their preparation, pharmaceutically acceptable salts thereof, their use as pharmaceuticals, pharmaceutical compositions containing one or more compounds of formula (I), and especially their use as C5a receptor modulators for treating e.g. vasculitis and inflammatory diseases.

  本发明涉及式(I)的衍生物，其中环A、X、Y、Z、RA、R1、R2、R3和R4如描述中所述。本发明公开了式(I)的衍生物，其中环A、X、Y、Z、RA、R1、R2、R3和R4如描述中所述，特别是例如2,4,6,7-四氢吡唑并[4,3-d]嘧啶-5-酮衍生物及相关化合物，它们的制备，其药学上可接受的盐，它们作为药物的用途，含有式(I)一个或多个化合物的药物组合物，特别是它们作为C5a受体调节剂用于治疗例如血管炎和炎症性疾病。
• The Influence of the 1-(3-Trifluoromethyl-Benzyl)-1H-Pyrazole-4-yl Moiety on the Adenosine Receptors Affinity Profile of Pyrazolo[4,3-e][1,2,4]Triazolo[1,5-c]Pyrimidine Derivatives
  作者：Stephanie Federico、Sara Redenti、Mattia Sturlese、Antonella Ciancetta、Sonja Kachler、Karl-Norbert Klotz、Barbara Cacciari、Stefano Moro、Giampiero Spalluto

  DOI：10.1371/journal.pone.0143504

  日期：——

  A new series of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine (PTP) derivatives has been developed in order to explore their affinity and selectivity profile at the four adenosine receptor subtypes. In particular, the PTP scaffold was conjugated at the C2 position with the 1-(3-trifluoromethyl-benzyl)-1H-pyrazole, a group believed to confer potency and selectivity toward the human (h) A2B adenosine receptor (AR) to the xanthine ligand 8-(1-(3-(trifluoromethyl)benzyl)-1H-pyrazol-4-yl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione (CVT 6975). Interestingly, the synthesized compounds turned out to be inactive at the hA2B AR but they displayed affinity at the hA3 AR in the nanomolar range. The best compound of the series (6) shows both high affinity (hA3 AR Ki = 11 nM) and selectivity (A1/A3 and A2A/A3 > 9090; A2B/A3 > 909) at the hA3 AR. To better rationalize these results, a molecular docking study on the four AR subtypes was performed for all the synthesized compounds. In addition, CTV 6975 and two close analogues have been subjected to the same molecular docking protocol to investigate the role of the 1-(3-trifluoromethyl-benzyl)-1H-pyrazole on the binding at the four ARs.

  为了探索在四种腺苷受体亚型上的亲和力和选择性谱，我们开发了一系列新的吡唑并[4,3-e][1,2,4]三唑并[1,5-c]嘧啶（PTP）衍生物。特别地，PTP骨架在C2位置与1-(3-三氟甲基苯基)-1H-吡唑结合，这一基团被认为赋予其对人类（h）A2B腺苷受体（AR）相对于黄嘌呤配体8-(1-(3-(三氟甲基)苯基)-1H-吡唑-4-基)-1,3-二甲基-1H-嘌呤-2,6(3H,7H)-二酮（CVT 6975）的效能和选择性。有趣的是，合成的化合物在hA2B AR上显示为无活性，但它们在hA3 AR上的亲和力却在纳摩尔范围内。该系列中表现最好的化合物（6）在hA3 AR上显示出高亲和力（hA3 AR Ki = 11 nM）和选择性（A1/A3和A2A/A3 > 9090；A2B/A3 > 909）。为了更好地解释这些结果，我们对所有合成化合物在四种AR亚型上进行了分子对接研究。此外，CTV 6975及其两个密切相关的类似物也进行了相同的分子对接协议，以调查1-(3-三氟甲基苯基)-1H-吡唑在四种AR之间结合的作用。