5-methyl-4-nitro-1H-pyrazole-3-amine | 76143-53-8

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 5-methyl-4-nitro-1H-pyrazole-3-amine
• 英文别名: 5-methyl-4-nitro-1(2)H-pyrazol-3-ylamine；5-methyl-4-nitro-1H-pyrazol-3-amine
• CAS: 76143-53-8
• 化学式: C₄H₆N₄O₂
• 分子量: 142.117
• InChiKey: ORPMTJVASAKZCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-methyl-4-nitro-1H-pyrazole-3-amine 在 盐酸 、 sodium acetate 、 sodium nitrite 作用下， 生成 1,3-bis-(5-methyl-4-nitro-1(2)H-pyrazol-3-yl)-triazene
  参考文献：
  名称：

  Musante, Gazzetta Chimica Italiana, 1946, vol. 76, p. 297,301

  摘要：

  DOI：
• 作为产物：
  描述：

  3-甲基-1,4-二硝基吡唑 在 氨 作用下， 以 乙醚 为溶剂， 反应 0.5h， 以97%的产率得到5-methyl-4-nitro-1H-pyrazole-3-amine
  参考文献：
  名称：

  C-核苷研究。第 XI 部分. 1,4-二硝基吡唑中的电影取代；硝基吡唑衍生物在合成福尔霉素中的应用

  摘要：

  1,4-二硝基-3-甲基吡唑与多种亲核试剂的反应导致通过电影取代过程形成5-取代的3-甲基-4-硝基吡唑11-15。该反应已被用作新合成福尔霉素的关键步骤。用氰化物离子处理 1,4-二硝基-3-(2,3,5-tri-O-乙酰基-β-D-呋喃核糖基)吡唑 (17) 产生 3(5)-氰基-4-硝基-5( 3)-(2,3,5-三-O-乙酰基-β-D-呋喃核糖基)吡唑(19)，产率为89%。催化还原为 4-氨基化合物 20 (84%)，随后与乙酸甲脒反应产生三乙酸甲霉素 21 (79%)。21 的甲醇分解以 90% 的产率生产了福尔霉素 (1)。

  DOI：

  10.1139/v80-419

文献信息

• Repair of sulfur mustard-induced DNA damage in mammalian cells measured by a host cell reactivation assay
  作者：Z. Matijasevic、M.L. Precopio、J.E. Snyder、D.B. Ludlum

  DOI：10.1093/carcin/22.4.661

  日期：2001.4

  DNA damage is thought to be the initial event that causes sulfur mustard (SM) toxicity, while the ability of cells to repair this damage is thought to provide a degree of natural protection. To investigate the repair process, we have damaged plasmids containing the firefly luciferase gene with either SM or its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES). Damaged plasmids were transfected into wild-type and nucleotide excision repair (NER) deficient Chinese hamster ovary cells; these cells were also transfected with a second reporter plasmid containing Renilla luciferase as an internal control on the efficiency of transfection. Transfected cells were incubated at 37°C for 27 h and then both firefly and Renilla luciferase intensities were measured on the same samples with the dual luciferase reporter assay. Bioluminescence in lysates from cells transfected with damaged plasmid, expressed as a percentage of the bioluminescence from cells transfected with undamaged plasmid, is increased by host cell repair activity. The results show that NER-competent cells have a higher reactivation capacity than NER-deficient cells for plasmids damaged by either SM or CEES. Significantly, NER-competent cells are also more resistant to the toxic effects of SM and CEES, indicating that NER is not only proficient in repairing DNA damage caused by either agent but also in decreasing their toxicity. This host cell repair assay can now be used to determine what other cellular mechanisms protect cells from mustard toxicity and under what conditions these mechanisms are most effective.

  DNA损伤被认为是引起硫芥(SM)毒性的起始事件，而细胞修复这种损伤的能力则被认为提供了一定程度的自然保护。为了研究修复过程，我们使用SM或其单功能类似物2-氯乙基乙基硫化物(CEES)对含有萤火虫荧光素酶基因的质粒进行了损伤。损伤后的质粒被转染到野生型和核苷酸切除修复(NER)缺陷的中国仓鼠卵巢细胞中；这些细胞还转染了第二个报告质粒，其中包含海肾荧光素酶作为转染效率的内部对照。转染后的细胞在37°C下孵育27小时，然后用双荧光素酶报告分析法在同一样本上测量萤火虫和海肾荧光素酶的强度。细胞裂解液中转染了损伤质粒的生物发光，以转染了未损伤质粒的细胞的生物发光的百分比表示，随宿主细胞修复活性而增加。结果显示，对于被SM或CEES损伤的质粒，具有NER能力的细胞比NER缺陷的细胞具有更高的再激活容量。值得注意的是，具有NER能力的细胞对SM和CEES的毒性影响也更具抵抗力，表明NER不仅擅长修复这两种试剂引起的DNA损伤，还能降低它们的毒性。现在，这种宿主细胞修复分析可以用来确定其他哪些细胞机制保护细胞免受芥子气毒性影响及其在这些机制最有效时的条件。
• MULTI-KINASE INHIBITOR COMPOUND, AND CRYSTAL FORM AND USE THEREOF
  申请人：Nanjing TransThera Biosciences Co. Ltd.

  公开号：US20190040064A1

  公开（公告）日：2019-02-07

  The present invention relates to a compound as represented by formula (I) or a pharmaceutically acceptable salt and stereoisomer thereof, wherein R1, R2, X, Y, P, W, and Ar are as defined in the description. The compound of formula (I) of the present invention can be used in the preparation of a drug for treating cancers mediated by abnormality of multi-kinases. Also provided is a crystal form I of a compound 4-(5-(2-chlorophenyl)-3-methyl-2,10-dihydropyrazolo[4,3-b]pyrido[4,3-e][1,4]diazepin-8-yl)morpholine, wherein in an X-ray powder diffraction pattern of crystal form I, there are characteristic peaks at 7.4±0.20, 17.9±0.2°, 18.9±0.2°, 19.4±0.2°, 21.5±0.2°, and 23.7±0.2°.

  本发明涉及一种由式（I）表示的化合物或其药用可接受的盐和立体异构体，其中R1、R2、X、Y、P、W和Ar如描述中定义。本发明的式（I）化合物可用于制备用于治疗由多激酶异常介导的癌症的药物。还提供了一种晶型I的化合物4-(5-(2-氯苯基)-3-甲基-2,10-二氢吡唑并[4,3-b]吡啶并[4,3-e][1,4]二氮杂环-8-基)吗啡啶，其中在晶型I的X射线粉末衍射图样中，在7.4±0.20、17.9±0.2°、18.9±0.2°、19.4±0.2°、21.5±0.2°和23.7±0.2°处有特征峰。
• [EN] CYCLIC COMPOUNDS AND METHODS OF USING SAME<br/>[FR] COMPOSÉS CYCLIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：SCHRODINGER INC

  公开号：WO2021134004A1

  公开（公告）日：2021-07-01

  The present application relates to compounds of Formula (I), as defined herein, and pharmaceutically acceptable salts thereof which are MALT1 inhibitors. The present application also describes pharmaceutical composition comprising a compound of Formula (I), and pharmaceutically acceptable salts thereof, and methods of using the compounds and compositions for treating diseases, such as cancer, autoimmune disorders, and inflammatory disorders.

  本申请涉及以下式（I）的化合物及其药用盐，其在此处定义为MALT1抑制剂。本申请还描述了包括式（I）化合物及其药用盐的药物组合物，以及使用这些化合物和组合物治疗疾病（如癌症、自身免疫性疾病和炎症性疾病）的方法。
• Base-induced ring cleavage of 4-functionalized-3-unsubstituted isoxazoles. Synthesis of 5-aminoazoles and 4-cyanoazoles
  作者：A. Alberola、L. F. Antolin、A. M. Gonzalez、M. A. Laguna、F. J. Pulido

  DOI：10.1002/jhet.5570230414

  日期：1986.7

  The base-induced ring cleavage of 4-nitro-(Ia), 4-ethoxycarbonyl- (Ib) and 4-acetyl-5-methylisoxazole (Ic) and the conversion of the resulting β-cyanoenolates and β-enaminonitriles into 5-aminoazoles and 4-cyanoazoles was studied.

  4-硝基-（Ia），4-乙氧基羰基-（Ib）和4-乙酰基-5-甲基异恶唑（Ic）的碱诱导的环裂解以及所得的β-氰基烯酸酯和β-烯腈转化为5-氨基唑并研究了4-氰基唑。
• Synthesis of Dinitro-Substituted Furans, Thiophenes, and Azoles
  作者：Alan Katritzky、Anatoliy Vakulenko、Jothilingam Sivapackiam、Bogdan Draghici、Reddy Damavarapu

  DOI：10.1055/s-2008-1032187

  日期：2008.3

  nitration of the corresponding mononitro furans with fuming nitric acid, thiophenes with acetyl nitrate, and thiazoles with trifluoroacetyl nitrate, gave dinitro-substituted furans, thiophenes, and thiazoles. The nitrations of 2-alkylthiophenes with 3 and 5 molar equivalents of acetyl nitrate, generated in situ, are discussed. Reactions of the mononitro furans with fuming nitric acid gave 1,1,5,5-tetrasubstituted

  相应的单硝基呋喃用发烟硝酸直接硝化，噻吩用乙酰硝酸酯直接硝化，噻唑用三氟乙酰硝酸酯直接硝化，得到二硝基取代的呋喃、噻吩和噻唑。讨论了原位生成的 2-烷基噻吩与 3 和 5 摩尔当量的乙酰硝酸酯的硝化反应。单硝基呋喃与发烟硝酸反应生成 1,1,5,5-四取代二氢呋喃作为副产物。用肼或其甲基或苯基衍生物处理 5-甲基-4-硝基异恶唑，然后用过氧化氢 (50%) 氧化相应的 4-氨基-5-硝基-1H-吡唑，得到 4,5-二硝基 -1H -吡唑。1-烷基-3,5-二硝基-1H-[1,2,4]三唑的安全一锅法合成是由双氰胺开发的。