4-氨基-5-乙基-1H-吡唑-3-羧酰胺 | 215298-74-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 4-氨基-5-乙基-1H-吡唑-3-羧酰胺
• 英文名称: 4-amino-3-ethyl-1H-pyrazole-5-carboxamide
• 英文别名: 4-amino-3-ethyl-1H-pyrazolo-5-carboxamide；4-amino-5-ethyl-1H-pyrazole-3-carboxamide
• CAS: 215298-74-1
• 化学式: C₆H₁₀N₄O
• mdl: MFCD09702199
• 分子量: 154.172
• InChiKey: YIAXJRMRAWYVOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  97.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-氨基-5-乙基-1H-吡唑-3-羧酰胺 在 4 A molecular sieve 、 caesium carbonate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 tert-butyl 3-[5-(5-acetyl-2-butoxy-3-pyridinyl)-3-ethyl-7-oxo-6,7-dihydro-2H-pyrazolo[4,3-d]pyrimidin-2-yl]-1-azetidinecarboxylate
  参考文献：
  名称：

  A Novel Series of Potent and Selective PDE5 Inhibitors with Potential for High and Dose-Independent Oral Bioavailability

  摘要：

  Sildenafil ( 5-[ 2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl) phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[ 4,3-d] pyrimidin-7-one), a potent and selective phosphodiesterase type 5 ( PDE5) inhibitor, provided the first oral treatment for male erectile dysfunction. The objective of the work reported in this paper was to combine high levels of PDE5 potency and selectivity with high and dose-independent oral bioavailability, to minimize the impact on the C-max of any interactions with coadministered drugs in the clinic. This goal was achieved through identification of a lower clearance series with a high absorption profile, by replacing the 5'-piperazine sulfonamide in the sildenafil template with a 5'-methyl ketone. This novel series provided compounds with low metabolism in human hepatocytes, excellent caco-2 flux, and the potential for good aqueous solubility. The in vivo oral and iv pharmacokinetic profiles of example compounds confirmed the high oral bioavailability predicted from these in vitro screens. 5-( 5-Acetyl-2-butoxy-3-pyridinyl)-3-ethyl-2-( 1-ethyl-3-azetidinyl)-2,6-dihydro-7H-pyrazolo[ 4,3-d] pyrimidin-7-one ( 2) was selected for progression into the clinic.

  DOI：

  10.1021/jm060113e
• 作为产物：
  描述：

  3-Ethyl-1H-pyrazole-5-carboxylic Acid 在 草酰氯 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 硝酸 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 28.0h， 生成 4-氨基-5-乙基-1H-吡唑-3-羧酰胺
  参考文献：
  名称：

  5-苯基吡唑并嘧啶酮 NPD-2975 针对具有更高抗锥虫疗效的化合物的先导优化

  摘要：

  非洲人类锥虫病 （HAT） 仍然面临很少的治疗选择和新出现的耐药性，这凸显了新型抗锥虫药物发现的紧迫性。在这里，我们描述了基于我们之前报道的优化命中 NPD-2975 （pIC50 7.2） 旨在提高抗锥虫功效和更好的理化特性的先导化合物优化工作。5-苯吡唑并嘧啶酮 NPD-2975 的系统修饰导致发现了 R4 取代的类似物 31c （NPD-3519），显示出更高的体外效力 （pIC50 7.8） 对布鲁氏锥虫和显着更好的代谢稳定性。此外，31c 的体内药代动力学评估和急性 T. brucei 小鼠模型中的实验证实，在 50 mg/kg 时口服生物利用度和抗锥虫疗效提高，没有明显的毒性。31c 具有良好的理化性质、低毒性、改进的药代动力学特征和体内疗效，可能成为未来 HAT 药物开发的有前途的候选药物。

  DOI：

  10.1021/acs.jmedchem.3c01976

文献信息

• Treatment of diabetic ulcers
  申请人：——

  公开号：US20030176442A1

  公开（公告）日：2003-09-18

  This invention relates to the use of cyclic guanosine 3′, 5′-monophosphate phosphodiesterase type five (cGMP PDE5) inhibitors, including in particular the compound sildenafil, for the treatment of diabetic ulcers, particularly diabetic foot ulcers.

  这项发明涉及使用环状鸟苷酸3′,5′-单磷酸磷酸二酯酶五型（cGMP PDE5）抑制剂，特别是硝苯地平这种化合物，用于治疗糖尿病溃疡，特别是糖尿病足溃疡。
• Novel process for the preparation of pyrazolopyrimidinones
  申请人：——

  公开号：US20020013465A1

  公开（公告）日：2002-01-31

  There is provided a process for the production a compound of general formula I: 1 wherein A, R 1 , R 2 , R 3 and R 4 have meanings given in the description, which process comprises the dehydrogenation of a compound of general formula II, 2

  提供了一种生产一般式I的化合物的过程：其中A、R1、R2、R3和R4具有描述中给出的含义，该过程包括对一般式II的化合物进行脱氢。
• Crystalline therapeutic agent
  申请人：——

  公开号：US20020040140A1

  公开（公告）日：2002-04-04

  A polymorph of 1-{6-ethoxy-5-[3-ethyl-6,7-dihydro-2-(2-methoxyethyl)-7-oxo-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-pyridylsulfonyl}-4-ethylpiperazine.

  1-{6-乙氧基-5-[3-乙基-6,7-二氢-2-(2-甲氧基乙基)-7-氧代-2H-吡唑并[4,3-d]嘧啶-5-基]-3-吡啶磺酰基}-4-乙基哌嗪的多晶形态。
• Treatments for female sexual dysfunction and methods for identifying compounds useful for treating female sexual dysfunction
  申请人：——

  公开号：US20030083228A1

  公开（公告）日：2003-05-01

  The present invention provides a method of treating female sexual dysfunction, the method comprising the step of administering to a patent, having or at risk of having one or more of the disorders or conditions associated with female sexual dysfunction, a therapeutically effective amount of a compound that attenuates the binding of agouti-related protein to melanocortin receptors, but does not attenuate the binding of &agr;-melanocyte stimulating hormone to melanocortin receptors. The present invention also provides a method of identifying a compound that is useful for the treatment or prevention of female sexual dysfunction, the method comprising the steps of: 1) determining if a compound affects the binding of agouti-related protein to melanocortin receptors; 2) determining if a compound affects the binding of &agr;-melanocyte stimulating hormone to melanocortin receptors; and 3) selecting a compound that attenuates the binding of agouti-related protein to melanocortin receptors, but does not affect the binding of &agr;-melanocyte stimulating hormone to melanocortin receptors.

  本发明提供了一种治疗女性性功能障碍的方法，该方法包括向患有或有可能患有与女性性功能障碍相关的一种或多种疾病或病况的患者施用一种治疗有效量的化合物，该化合物减弱了agouti相关蛋白与黑素皮质素受体的结合，但不影响α-黑素细胞刺激激素与黑素皮质素受体的结合。本发明还提供了一种识别对治疗或预防女性性功能障碍有用的化合物的方法，该方法包括以下步骤：1）确定化合物是否影响agouti相关蛋白与黑素皮质素受体的结合；2）确定化合物是否影响α-黑素细胞刺激激素与黑素皮质素受体的结合；以及3）选择一种减弱agouti相关蛋白与黑素皮质素受体结合的化合物，但不影响α-黑素细胞刺激激素与黑素皮质素受体的结合。
• Methods of treatment and kits comprising a growth hormone secretagogue
  申请人：——

  公开号：US20030105114A1

  公开（公告）日：2003-06-05

  The present invention relates to methods of treating bulimia nervosa, male erectile dysfunction, female sexual dysfunction, thyroid cancer, breast cancer, or ameliorating ischemic nerve or muscle damage. The present invention also relates to kits that can be used in the treatment of bulimia nervosa, male erectile dysfunction, female sexual dysfunction, thyroid cancer, breast cancer, or ameliorating ischemic nerve or muscle damage. The present invention further relates to increasing gastrointestinal motility after surgery and increasing gastrointestinal motility in patients who have been administered an agent that decreases gastrointestinal motility.

  本发明涉及治疗厌食症、男性勃起功能障碍、女性性功能障碍、甲状腺癌、乳腺癌或改善缺血性神经或肌肉损伤的方法。本发明还涉及可用于治疗厌食症、男性勃起功能障碍、女性性功能障碍、甲状腺癌、乳腺癌或改善缺血性神经或肌肉损伤的试剂盒。本发明还涉及术后增加胃肠道蠕动和在接受降低胃肠道蠕动试剂的患者中增加胃肠道蠕动。