4-(2-ethoxybenzamido)-3-n-propyl-1H-pyrazolo-5-carboxamide | 139756-10-8

• 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: 4-(2-ethoxybenzamido)-3-n-propyl-1H-pyrazolo-5-carboxamide
• 英文别名: 4-(2-Ethoxybenzamido)-3-n-propylpyrazole-5-carboxamide；4-[(2-ethoxybenzoyl)amino]-5-propyl-1H-pyrazole-3-carboxamide
• CAS: 139756-10-8
• 化学式: C₁₆H₂₀N₄O₃
• 分子量: 316.36
• InChiKey: HHLIJPUCDKECCR-UHFFFAOYSA-N

物化性质

• 沸点：
  466.3±45.0 °C(Predicted)
• 密度：
  1.273±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-ethoxybenzamido)-3-n-propyl-1H-pyrazolo-5-carboxamide 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 5-(2-乙氧基苯基)-3-丙基-1,6-二氢-7H-吡唑并[4,3-d]嘧啶-7-酮
  参考文献：
  名称：

  比较不同的杂环骨架作为底物类似物PDE5抑制剂。

  摘要：

  比较了几种不同的杂环系统作为PDE5抑制剂支架。除了已知的3H-咪唑并[5,1-f] [1,2,4]三嗪-4-酮和吡唑并吡喃二酮外，咪唑并[1,5-a] [1,3,5]三嗪-4（ 3H）-一也被证明是具有体内活性的有效的和选择性的PDE抑制剂支架。阐明了在不同支架上具有普遍性的磺酰胺衍生物的SAR趋势。

  DOI：

  10.1016/j.bmcl.2005.05.090
• 作为产物：
  描述：

  2-乙氧基苯甲酸 在 氨 、 三乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 水 、 1,2-二氯乙烷 为溶剂， 反应 72.33h， 生成 4-(2-ethoxybenzamido)-3-n-propyl-1H-pyrazolo-5-carboxamide
  参考文献：
  名称：

  Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs

  摘要：

  Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and wellbeing in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this Letter we describe target repurposing efforts focused on trypanosomal phosphodiesterases. We outline the synthesis and biological evaluation of analogs of sildenafil (1), a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We find that, while low potency analogs can be prepared, this chemical class is a sub-optimal starting point for further development of TbrPDE inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.119

文献信息

• Comparison of different heterocyclic scaffolds as substrate analog PDE5 inhibitors
  作者：Helmut Haning、Ulrich Niewöhner、Thomas Schenke、Thomas Lampe、Alexander Hillisch、Erwin Bischoff

  DOI：10.1016/j.bmcl.2005.05.090

  日期：2005.9

  Several different heterocyclic systems were compared as PDE5 inhibitor scaffolds. In addition to the known 3H-imidazo[5,1-f][1,2,4]triazin-4-ones and pyrazolopyrimidinones, isomeric imidazo[1,5-a][1,3,5]triazin-4(3H)-ones were also shown to be potent and selective PDE inhibitor scaffolds with in vivo activity. SAR trends were elucidated for sulfonamide derivatives with generality across different scaffolds

  比较了几种不同的杂环系统作为PDE5抑制剂支架。除了已知的3H-咪唑并[5,1-f] [1,2,4]三嗪-4-酮和吡唑并吡喃二酮外，咪唑并[1,5-a] [1,3,5]三嗪-4（ 3H）-一也被证明是具有体内活性的有效的和选择性的PDE抑制剂支架。阐明了在不同支架上具有普遍性的磺酰胺衍生物的SAR趋势。
• Method of treating a patient having precancerous lesions with phenyl purinone derivatives
  申请人：Cell Pathways, Inc.

  公开号：US06200980B1

  公开（公告）日：2001-03-13

  Derivatives of Phenyl Purinone are useful for the treatment of patients having precancerous lesions. These compounds are also useful to inhibit growth of neoplastic cells.

  苯基嘌呤酮衍生物对于治疗患有癌前病变的患者非常有用。这些化合物还可用于抑制肿瘤细胞的生长。
• Pyrazolopyrimidinone antianginal agents
  申请人：Pfizer Inc.

  公开号：US05250534A1

  公开（公告）日：1993-10-05

  Compounds of the formula: ##STR1## wherein R.sup.1 is H, C.sub.1 -C.sub.3 alkyl, C.sub.3 -C.sub.5 cycloalkyl or C.sub.1 -C.sub.3 perfluoroalkyl; R.sup.2 is H, C.sub.1 -C.sub.6 alkyl optionally substituted by OH, C.sub.1 -C.sub.3 alkoxy or C.sub.3 -C.sub.6 cycloalkyl, or C.sub.1 -C.sub.3 perfluoroalkyl; R.sup.3 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.6 alkynyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 perfluoroalkyl or (C.sub.3 -C.sub.6 cycloalkyl)C.sub.1 -C.sub.6 alkyl; R.sup.4 taken together with the nitrogen atom to which it is attached completes a pyrrolidinyl, piperidino, morpholino, or 4-N-(R.sup.6)-piperazinyl group; R.sup.5 is H, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.3 alkoxy, NR.sup.7 R.sup.8, or CONR.sup.7 R.sup.8 ; R.sup.6 is H, C.sub.1 -C.sub.6 alkyl, (C.sub.1 -C.sub.3 alkoxy) C.sub.2 - C.sub.6 alkyl, hydroxy C.sub.2 -C.sub.6 alkyl, (R.sup.7 R.sup.8 N)C.sub.2 -C.sub.6 alkyl, (R.sup.7 R.sup.8 NCO)C.sub.1 -C.sub.6 alkyl, CONR.sup.7 R.sup.8, CSNR.sup.7 R.sup.8 or C(NH)NR.sup.7 R.sup.8 ; R.sup.7 and R.sup.8 are each independently H, C.sub.1 -C.sub.4 alkyl, (C.sub.1 -C.sub.3 alkoxy)C.sub.2 -C.sub.4 alkyl or hydroxy C.sub.2 -C.sub.4 alkyl; and pharmaceutically acceptable salts thereof, are selective cGMP PDE inhibitors useful in the treatment of cardiovascular disorders such as angina, hypertension, heart failure and atherosclerosis.

  该化合物的结构式为：##STR1## 其中R.sup.1为H，C.sub.1 -C.sub.3烷基，C.sub.3 -C.sub.5环烷基或C.sub.1 -C.sub.3全氟烷基；R.sup.2为H，C.sub.1 -C.sub.6烷基，可以选择性地被OH，C.sub.1 -C.sub.3烷氧基或C.sub.3 -C.sub.6环烷基，或C.sub.1 -C.sub.3全氟烷基取代；R.sup.3为C.sub.1 -C.sub.6烷基，C.sub.3 -C.sub.6烯基，C.sub.3 -C.sub.6炔基，C.sub.3 -C.sub.7环烷基，C.sub.1 -C.sub.6全氟烷基或(C.sub.3 -C.sub.6环烷基)C.sub.1 -C.sub.6烷基；R.sup.4与其连接的氮原子一起形成吡咯啉基、哌啶基、吗啉基或4-N-(R.sup.6)-哌嗪基；R.sup.5为H，C.sub.1 -C.sub.4烷基，C.sub.1 -C.sub.3烷氧基，NR.sup.7 R.sup.8，或CONR.sup.7 R.sup.8；R.sup.6为H，C.sub.1 -C.sub.6烷基，(C.sub.1 -C.sub.3烷氧基)C.sub.2 - C.sub.6烷基，羟基C.sub.2 -C.sub.6烷基，(R.sup.7 R.sup.8 N)C.sub.2 -C.sub.6烷基，(R.sup.7 R.sup.8 NCO)C.sub.1 -C.sub.6烷基，CONR.sup.7 R.sup.8，CSNR.sup.7 R.sup.8或C(NH)NR.sup.7 R.sup.8；R.sup.7和R.sup.8各自独立地为H，C.sub.1 -C.sub.4烷基，(C.sub.1 -C.sub.3烷氧基)C.sub.2 -C.sub.4烷基或羟基C.sub.2 -C.sub.4烷基；以及其药学上可接受的盐，是用于治疗心血管疾病如心绞痛、高血压、心力衰竭和动脉粥样硬化的选择性cGMP PDE抑制剂。
• Pyrazolopyrimidinones which inhibit type 5 cyclic guanosine 3',5'-monophosphate phosphodiesterase (cGMP-PDE5) for the treatment of sexual dysfunction
  申请人：Pfizer Inc

  公开号：US20040180944A1

  公开（公告）日：2004-09-16

  1 Compounds of formulae (IA) and (IB) or pharmaceutically or veterinarily acceptable salts thereof, or pharmaceutically or veterinarily acceptable solvates of either entity, wherein R 1 is C 1 to C 3 alkyl substituted with C 3 to C 6 cycloalkyl, CONR 5 R 6 or a N-linked heterocyclic group; (CH 2 ) n Het or (CH 2 ) n Ar, R 2 is C 1 to C 6 alkyl; R 3 is C 1 to C 6 alkyl optionally substituted with C 1 to C 4 alkoxy; R 4 is SO 2 NR 7 R 8 ; R 5 and R 6 are each independently selected from H and C 1 to C 4 alkyl optionally substituted with C 1 to C 4 alkoxy, or, together with the nitrogen atom to which they are attached, form a 5- or 6-membered heterocyclic group; R 7 and R 8 , together with the nitrogen atom to which they are attached, form a 4-R 10 -piperazinyl group; R 10 is H or C 1 to C 4 alkyl optionally substituted with OH, C 1 to C 4 alkoxy or CONH 2 ; Het is an optionally substituted C-linked 5- or 6-membered heterocyclic group; Ar is optionally substituted phenyl; and n is 0 or 1; are potent and selective cGMP PDE5 inhibitors useful in the treatment of, inter alia, male erectile dysfunction and female sexual dysfunction.

  式（IA）和（IB）化合物或其药学上或兽医学上可接受的盐，或者是任一实体的药学上或兽医学上可接受的溶剂化合物，其中R1是C1到C3烷基，其上取代了C3到C6环烷基，CONR5R6或N-连接的杂环基；（CH2）nHet或（CH2）nAr，R2是C1到C6烷基；R3是C1到C6烷基，可选地取代了C1到C4烷氧基；R4是SO2NR7R8；R5和R6各自独立地选择自H和C1到C4烷基，可选地取代自C1到C4烷氧基，或者与它们所连接的氮原子一起形成一个5-或6-成员的杂环基；R7和R8与它们所连接的氮原子一起形成一个4-R10-哌嗪基团；R10是H或C1到C4烷基，可选地取代自OH、C1到C4烷氧基或CONH2；Het是可选地取代的C-连接的5-或6-成员的杂环基；Ar是可选地取代的苯基；n为0或1；这些化合物是强效和选择性的cGMP PDE5抑制剂，可用于治疗男性勃起功能障碍和女性性功能障碍等疾病。
• Pyrazolopyrimidinone cGMP PDE5 inhibitors for the treatment of sexual dysfunction
  申请人：PFIZER INC.

  公开号：EP0995750A1

  公开（公告）日：2000-04-26

  There is provided compounds of formula IA and of formula IB, wherein R1, R2, R3, R4 and A have meanings given in the description, which are useful in the curative and prophylactic treatment of a medical condition for which inhibition of a cyclic guanosine 3',5'-monophosphate phosphodiesterase (e.g. cGMP PDE5) is desired.

  提供了式 IA 和式 IB 的化合物、 其中 R1、R2、R3、R4 和 A 具有描述中给出的含义，可用于治疗和预防需要抑制环鸟苷-3',5'-单磷酸磷酸二酯酶（如 cGMP PDE5）的病症。