N-(4-bromophenyl)-1-carbamimidamidomethanimidamide hydrochloride | 19579-40-9

• 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: N-(4-bromophenyl)-1-carbamimidamidomethanimidamide hydrochloride
• 英文别名: BIGUANIDE, 1-(p-BROMOPHENYL)-, MONOHYDROCHLORIDE；[N'-(4-bromophenyl)carbamimidoyl]-(diaminomethylidene)azanium;chloride
• CAS: 19579-40-9
• 化学式: C₈H₁₀BrN₅*ClH
• 分子量: 292.566
• InChiKey: ZJYQMWQDOBAABA-UHFFFAOYSA-N

物化性质

• 熔点：
  242-244 °C

计算性质

• 辛醇/水分配系数(LogP)：
  1.09
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  103
• 氢给体数：
  4
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-(4-bromophenyl)-1-carbamimidamidomethanimidamide hydrochloride 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 22.0h， 生成 N-(4-bromophenyl)-1-carbamimidamidomethanimidamide
  参考文献：
  名称：

  [EN] NOVEL CYCLIC GMP-AMP SYNTHASE (CGAS) INHIBITORS AND THEIR METHOD OF USE
  [FR] NOUVEAUX INHIBITEURS CYCLIQUES DE LA GMP-AMP SYNTHASE (CGAZ) ET LEUR PROCÉDÉ D'UTILISATION

  摘要：

  公开号：

  WO2019241787A9
• 作为产物：
  描述：

  二聚氰胺 、 4-溴苯胺 在 盐酸 作用下， 以 水 、 仲丁醇 为溶剂， 反应 24.0h， 以88%的产率得到N-(4-bromophenyl)-1-carbamimidamidomethanimidamide hydrochloride
  参考文献：
  名称：

  使用多药理学浏览器PPB2从表型筛选中鉴定溶血磷脂酸酰基转移酶β（LPAAT-β）为纳摩尔血管生成抑制剂的靶标。

  摘要：

  通过在表型共培养测定中筛选激酶抑制剂类似物的聚焦库以抑制血管生成，我们确定了一种氨基三嗪，它可作为一种抑制细胞生长的纳摩尔抑制剂。但是，发现该氨基三嗪在全基因组谱分析中完全没有活性。为了解释其作用机理，我们使用了在线靶标预测工具PPB2（http://ppb2.gdb.tools），该工具建议溶血磷脂酸酰基转移酶β（LPAAT-β）作为该氨基三嗪和其他类似物的可能靶标。通过结构-活动关系分析来识别。与已知的LPAAT-β抑制剂相比，在生化分析中证实了LPAAT-β抑制（IC50≈15 nm），并且抑制了它对细胞增殖的作用。

  DOI：

  10.1002/cmdc.201800554

文献信息

• Discovery of Small-Molecule Cyclic GMP-AMP Synthase Inhibitors
  作者：Rosaura Padilla-Salinas、Lijun Sun、Rachel Anderson、Xikang Yang、Shuting Zhang、Zhijian J. Chen、Hang Yin

  DOI：10.1021/acs.joc.9b02666

  日期：2020.2.7

  exists for inhibiting cGAS in cells, while others are limited by their poor cellular activity or specificity, which underscores the urgency for discovering new cGAS inhibitors. Here, we describe the development of new small-molecule human cGAS (hcGAS) inhibitors (80 compounds synthesized) with high binding affinity in vitro and cellular activity. Our studies show CU-32 and CU-76 selectively inhibit the DNA

  环鸟苷单磷酸腺苷单磷酸（GMP-AMP）（cGAS）是一种胞质DNA传感器，在I型干扰素应答中起着重要作用。来自入侵微生物或自身来源的DNA触发cGAS的酶促活性。cGAS的异常激活与各种自身免疫性疾病有关。仅存在一种抑制细胞中cGAS的选择性探针，而另一些选择性探针由于其细胞活性或特异性差而受到限制，这突显了发现新的cGAS抑制剂的紧迫性。在这里，我们描述了具有高结合亲和力的体外和细胞活性的新型小分子人cGAS（hcGAS）抑制剂（合成的80种化合物）的开发。我们的研究表明CU-32和CU-76选择性抑制人细胞中的DNA途径，但对RIG-I-MAVS或Toll样受体途径没有影响。
• [EN] HETEROARYL COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS HÉTÉROARYLE ET LEUR UTILISATION
  申请人：MINORYX THERAPEUTICS S L

  公开号：WO2018122775A1

  公开（公告）日：2018-07-05

  The application is directed to compounds of formula (I): and their salts and solvates, wherein R1, R2, R3, A1, A2, A3, and n are as set forth in the specification, as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of a lysosomal storage disease, such as Gaucher's, and other diseases or disorders that are synucleinopathies.

  该申请涉及式(I)的化合物及其盐和溶剂合物，其中R1、R2、R3、A1、A2、A3和n如规范中所述，以及它们的制备方法，包含它们的药物组合物，以及用于治疗和/或预防溶酶体贮积病（如高雪氏病）和其他α-突触核蛋白病的用途。
• AN EFFICIENT SYNTHESIS OF 1-ARYL-4,6-DIAMINO-1,2-DIHYDRO- 1,3,5-TRIAZINES
  作者：Neungruthai Saesaengseerung、Tirayut Vilaivan、Yodhathai Thebtaranonth

  DOI：10.1081/scc-120005415

  日期：2002.1.1

  ABSTRACT 1-Aryl-4,6-diamino-1,2-dihydro-1,3,5-triazines bearing diverse substituents at C2 and on the aromatic ring have been synthesized in good yield from an acid-catalyzed reaction between corresponding arylbiguanide and carbonyl compound in the presence of triethyl orthoacetate as a water scavenger.

  摘要 1-Aryl-4,6-diamino-1,2-dihydro-1,3,5-triazines 在 C2 和芳环上具有不同的取代基，通过相应的芳基双胍和芳环之间的酸催化反应合成，收率良好。在作为水清除剂的原乙酸三乙酯存在下羰基化合物。
• Biguanide compound and use thereof
  申请人：ImmunoMet Therapeutics Inc.

  公开号：US10626085B2

  公开（公告）日：2020-04-21

  The present invention relates to a guanidine compound and a use thereof, and more specifically, to a guanidine derivative showing excellent effects of inhibiting cancer cell proliferation, cancer metastasis, and cancer recurrence; a preparation method thereof; and a pharmaceutical composition containing the same as an active ingredient. Compared to existing drugs, the guanidine derivative according to the present invention shows excellent effects of inhibiting cancer cell proliferation, cancer metastasis, and cancer recurrence even with small doses, and may thus be effectively used in preventing or treating various cancers such as uterine cancer, breast cancer, stomach cancer, brain cancer, rectal cancer, colorectal cancer, lung cancer, skin cancer, blood cancer, liver cancer, etc., inhibiting cancer cell proliferation and cancer metastasis.

  本发明涉及一种胍类化合物及其用途，更具体地说，涉及一种在抑制癌细胞增殖、癌症转移和癌症复发方面具有卓越效果的胍类衍生物；其制备方法；以及一种以其为有效成分的药物组合物。与现有药物相比，根据本发明的胍类衍生物即使剂量很小，也能显示出极佳的抑制癌细胞增殖、癌转移和癌症复发的效果，因此可有效用于预防或治疗各种癌症，如子宫癌、乳腺癌、胃癌、脑癌、直肠癌、大肠癌、肺癌、皮肤癌、血癌、肝癌等，抑制癌细胞增殖和癌转移。
• Synthesis of Solution-Phase Combinatorial Library of 4,6-Diamino-1,2-dihydro-1,3,5-triazine and Identification of New Leads Against A16V+S108T Mutant Dihydrofolate Reductase of Plasmodium falciparum
  作者：Tirayut Vilaivan、Neungruthai Saesaengseerung、Deanpen Jarprung、Sumalee Kamchonwongpaisan、Worachart Sirawaraporn、Yongyuth Yuthavong

  DOI：10.1016/s0968-0896(02)00344-9

  日期：2003.1

  An efficient method to synthesize solution-phase combinatorial library of 1-aryl-4,6-diamino-1,2-dihydro-1,3,5-triazine was developed. The strategy involved an acid-catalyzed cyclocondensation between arylbiguanide hydrochlorides and carbonyl compounds in the presence of triethyl orthoacetate as water scavenger. A 96-membered combinatorial library was constructed from 6 aryl biguanides and 16 carbonyl compounds. Screening of the library by iterative deconvolution method revealed two candidate leads which are equally active against wild-type Plasmodium falciparum dihydrofolate reductase, but are about 100-fold more effective against the A16V + S108T mutant enzyme as compared to cycloguanil. (C) 2002 Elsevier Science Ltd. All rights reserved.