N-cyclopropyl-5-nitrothiophene-2-carboxamide | 1017220-14-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: N-cyclopropyl-5-nitrothiophene-2-carboxamide
• CAS: 1017220-14-2
• 化学式: C₈H₈N₂O₃S
• mdl: MFCD10564856
• 分子量: 212.229
• InChiKey: VHTMZSKNDOSLRE-UHFFFAOYSA-N

物化性质

• 沸点：
  418.4±30.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.375
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-cyclopropyl-5-nitrothiophene-2-carboxamide 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium phosphate monohydrate 、 20 % Pd(OH)2/C 、 bis(2',6'-diisopropoxybiphenyl)cyclohexylphosphine 、 氢气 作用下， 以 乙醇 、 叔丁醇 为溶剂， 120.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 N-cyclopropyl-5-(4-chloro-6-fluoro-2-methyl-1H-benzo[d]imidazol-1-yl)thiophene-2-carboxamide
  参考文献：
  名称：

  Optimization of Potent Inhibitors of P. falciparum Dihydroorotate Dehydrogenase for the Treatment of Malaria

  摘要：

  Inhibition of dihydroorotate dehydrogenase (DHODH) for P. falciparum potentially represents a new treatment option for malaria, since DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and P. falciparum is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. We report herein the synthesis and structure-activity relationship of a series of 5-(2-methylbenzimidazol-1-yl)-N-alkylthiophene-2-carboxamides that are potent inhibitors against PfDHODH but do not inhibit the human enzyme. On the basis of efficacy observed in three mouse models of malaria, acceptable safety pharmacology risk assessment and safety toxicology profile in rodents, lack of potential drug-drug interactions, acceptable ADME/pharmacokinetic profile, and projected human dose, 5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)-N-cyclopropylthiophene-2-carboxamide 2q was identified as a potential drug development candidate.

  DOI：

  10.1021/ml200143c
• 作为产物：
  描述：

  5-硝基噻吩-2-甲酸 在 氯化亚砜 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 0.5h， 生成 N-cyclopropyl-5-nitrothiophene-2-carboxamide
  参考文献：
  名称：

  Optimization of Potent Inhibitors of P. falciparum Dihydroorotate Dehydrogenase for the Treatment of Malaria

  摘要：

  Inhibition of dihydroorotate dehydrogenase (DHODH) for P. falciparum potentially represents a new treatment option for malaria, since DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and P. falciparum is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. We report herein the synthesis and structure-activity relationship of a series of 5-(2-methylbenzimidazol-1-yl)-N-alkylthiophene-2-carboxamides that are potent inhibitors against PfDHODH but do not inhibit the human enzyme. On the basis of efficacy observed in three mouse models of malaria, acceptable safety pharmacology risk assessment and safety toxicology profile in rodents, lack of potential drug-drug interactions, acceptable ADME/pharmacokinetic profile, and projected human dose, 5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)-N-cyclopropylthiophene-2-carboxamide 2q was identified as a potential drug development candidate.

  DOI：

  10.1021/ml200143c

文献信息

• Substituted oxopyridine derivatives
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US10421742B2

  公开（公告）日：2019-09-24

  The invention relates to substituted oxopyridine derivatives and to processes for their preparation, and also to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular cardiovascular disorders, preferably thrombotic or thromboembolic disorders, and oedemas, and also ophthalmic disorders.

  本发明涉及取代的氧吡啶衍生物及其制备工艺，还涉及其用于制备治疗和/或预防疾病的药物，尤其是心血管疾病，最好是血栓性或血栓栓塞性疾病和水肿，以及眼科疾病。
• Design and Synthesis of Dual-Target Inhibitors Targeting Androgen Receptors and Glucocorticoid Receptors to Overcome Antiandrogen Resistance in Castration-Resistant Prostate Cancer
  作者：Chenfan Li、Xiaoli Han、Qiuxia Yan、Yang Ji、Rongyu Zhang、Dazhong Yuan、Fulian Yang、Jianlong Wang、Meng Wu、Jinming Zhou

  DOI：10.1021/acs.jmedchem.3c01668

  日期：2024.3.14

  Androgen receptor (AR) antagonists play important roles in the treatment of castration-resistant prostate cancer (CRPC). The glucocorticoid receptor (GR) upregulation leads to drug resistance for clinically used antiandrogens. Therefore, blocking AR/GR signaling simultaneously has become an efficient strategy to overcome the drug resistance of CRPC. Our previous work indicated that Z19 could inhibit

  雄激素受体（AR）拮抗剂在去势抵抗性前列腺癌（CRPC）的治疗中发挥着重要作用。糖皮质激素受体（GR）上调会导致临床使用的抗雄激素产生耐药性。因此，同时阻断AR/GR信号已成为克服CRPC耐药性的有效策略。我们之前的工作表明Z19可以抑制AR和GR的活性。在此，我们优化了Z19的结构，并将GA32鉴定为有效的 AR/GR 双重抑制剂。 GA32有效降低 AR/GR 下游基因的 mRNA 和蛋白质水平。 GA32在体外和体内均能有效抑制恩杂鲁胺耐药性 CRPC 的增殖。 GA32可以直接与AR和GR结合，并且预测的GA32与AR/GR的结合模式表明GA32与AR或GR激素结合口袋结合。这项工作提供了一种具有双重 AR/GR 抑制活性的潜在先导化合物，以克服 CRPC 的耐药性。
• SUBSTITUTED OXOPYRIDINE DERIVATIVES
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：EP3319956B1

  公开（公告）日：2021-01-06
• Optimization of Potent Inhibitors of <i>P. falciparum</i> Dihydroorotate Dehydrogenase for the Treatment of Malaria
  作者：Renato T. Skerlj、Cecilia M. Bastos、Michael L. Booker、Martin L. Kramer、Robert H. Barker、Cassandra A. Celatka、Thomas J. O’Shea、Benito Munoz、Amar Bir Sidhu、Joseph F. Cortese、Sergio Wittlin、Petros Papastogiannidis、Inigo Angulo-Barturen、Maria Belen Jimenez-Diaz、Edmund Sybertz

  DOI：10.1021/ml200143c

  日期：2011.9.8

  Inhibition of dihydroorotate dehydrogenase (DHODH) for P. falciparum potentially represents a new treatment option for malaria, since DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and P. falciparum is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. We report herein the synthesis and structure-activity relationship of a series of 5-(2-methylbenzimidazol-1-yl)-N-alkylthiophene-2-carboxamides that are potent inhibitors against PfDHODH but do not inhibit the human enzyme. On the basis of efficacy observed in three mouse models of malaria, acceptable safety pharmacology risk assessment and safety toxicology profile in rodents, lack of potential drug-drug interactions, acceptable ADME/pharmacokinetic profile, and projected human dose, 5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)-N-cyclopropylthiophene-2-carboxamide 2q was identified as a potential drug development candidate.