4-[2-ethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-ylcarboxamido]-3-ethyl-2-(1-methylpiperidin-4-yl)pyrazole-5-carboxamide | 334828-39-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-[2-ethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-ylcarboxamido]-3-ethyl-2-(1-methylpiperidin-4-yl)pyrazole-5-carboxamide
• 英文别名: N-[3-carbamoyl-5-ethyl-1-(1-methylpiperidin-4-yl)pyrazol-4-yl]-2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridine-3-carboxamide
• CAS: 334828-39-6
• 化学式: C₂₆H₄₀N₈O₅S
• 分子量: 576.72
• InChiKey: ZIQKEGFLCSLVPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  164
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-[2-ethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-ylcarboxamido]-3-ethyl-2-(1-methylpiperidin-4-yl)pyrazole-5-carboxamide 、 正丁醇 在 双(三甲基硅烷基)氨基钾 作用下， 以 乙酸乙酯 为溶剂， 反应 6.0h， 以50%的产率得到5-[2-n-butoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-yl]-3-ethyl-2-(1-methylpiperidin-4-yl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
  参考文献：
  名称：

  The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics

  摘要：

  This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profile resulted in the identification of UK-369003 (19a) and its nomination as a clinical candidate. The clinical pharmacokinetic and safety profile has enabled us to progress the compound to test its efficacy in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and a paper describing its efficacy has recently been published. 2,3 (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.022
• 作为产物：
  描述：

  Tert-butyl 4-[3-carbamoyl-4-[[2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridine-3-carbonyl]amino]-5-ethylpyrazol-1-yl]piperidine-1-carboxylate 在 双(三甲基硅烷基)氨基钾 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 24.5h， 生成 4-[2-ethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-ylcarboxamido]-3-ethyl-2-(1-methylpiperidin-4-yl)pyrazole-5-carboxamide
  参考文献：
  名称：

  The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics

  摘要：

  This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profile resulted in the identification of UK-369003 (19a) and its nomination as a clinical candidate. The clinical pharmacokinetic and safety profile has enabled us to progress the compound to test its efficacy in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and a paper describing its efficacy has recently been published. 2,3 (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.022

文献信息

• 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。
• Treatment of neuropathy
  申请人：——

  公开号：US20030162782A1

  公开（公告）日：2003-08-28

  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 neuropathy, including in particular the treatment of diabetic neuropathy.

  这项发明涉及使用环鸟苷3′,5′-单磷酸磷酸二酯酶五型（cGMP PDE5）抑制剂，特别是包括化合物西地那非，用于治疗神经病变，特别是治疗糖尿病神经病变。
• Compositions and methods of treatment for conditions responsive to testosterone elevation
  申请人：——

  公开号：US20030114440A1

  公开（公告）日：2003-06-19

  This invention relates to methods and pharmaceutical compositions useful in the treatment of conditions that are responsive to the elevation of testosterone levels in the body and the use of estrogen agonists/antagonists for the manufacture of medicaments for the treatment of conditions that are responsive to the elevation of testosterone levels in the body. The compositions are comprised of an estrogen agonist/antagonist and a pharmaceutically acceptable vehicle, carrier or diluent. These compositions are effective in treating male subject sexual dysfunction and timidity in female subjects including post-menopausal women and are effective in increasing libido in female subjects including post-menopausal women. In the case of male subject sexual dysfunction, the compositions may also include a compound which is an elevator of cyclic guanosine 3′,5′-monophosphate (cGMP). Additionally, the compositions are effective in other conditions whose etiology is a result of testosterone deficiency or which can be ameliorated by increasing testosterone levels within the body. Methods of the invention include the treatment of conditions that are responsive to elevation of testosterone levels such as treating male subject sexual dysfunction and timidity in female subjects including post-menopausal women and the increase of libido of female subjects including post-menopausal women. The methods of treatment are effective while substantially reducing the concomitant liability of adverse effects associated with testosterone administration.

  本发明涉及用于治疗对体内睾酮水平升高有反应的疾病的方法和制药组合物，以及使用雌激素激动剂/拮抗剂制造治疗对体内睾酮水平升高有反应的疾病的药物。该组合物由雌激素激动剂/拮抗剂和药学上可接受的载体、载体或稀释剂组成。这些组合物对治疗男性主体性功能障碍和女性主体包括绝经后妇女的胆怯症状有效，并且对增加女性主体包括绝经后妇女的性欲有效。对于男性主体性功能障碍的情况，该组合物还可以包括一种升高环磷鸟苷酸3'，5'-单磷酸（cGMP）的化合物。此外，该组合物对其他疾病的疗效是通过睾酮缺乏引起的或可以通过提高体内睾酮水平来改善的。本发明的方法包括治疗对睾酮水平升高有反应的疾病，如治疗男性主体性功能障碍和女性主体包括绝经后妇女的胆怯症状以及增加女性主体包括绝经后妇女的性欲。该治疗方法在显著降低睾酮治疗的不良反应同时具有疗效。
• Pharmaceutically active compounds
  申请人：Pfizer Inc.

  公开号：US20040152712A1

  公开（公告）日：2004-08-05

  Compounds of the formula (1): 1 wherein R 1 , R 2 , R 4 and R 13 are as defined or a pharmaceutically or veterinarily acceptable salt or polymorph thereof, or a pharmaceutically or veterinarily acceptable solvate or pro-drug thereof: are potent and selective inhibitors of type 5 cyclic guanosine 3′,5′-monophosphate phosphodiestbrase (cGMP PDE5) and have utility in the treatment of, inter alia, male erectile dysfunction (MED) and female sexual dysfunction (FSD).

  化合物的式子为(1): 1，其中R1、R2、R4和R13如定义所述，或其药学或兽医学上可接受的盐或多晶形式，或其药学或兽医学上可接受的溶剂或前药形式：是强效和选择性的5型环鸟苷酸3′，5′-单磷酸磷酸二酯酶（cGMP PDE5）抑制剂，并在治疗男性勃起功能障碍（MED）和女性性功能障碍（FSD）等方面具有用途。