5-{5-[4-(2-hydroxyethyl)piperazinylsulfonyl]-2-n-propoxyphenyl}-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one | 139755-87-6

• 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: 5-{5-[4-(2-hydroxyethyl)piperazinylsulfonyl]-2-n-propoxyphenyl}-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
• 英文别名: 5-{5-[4-(2-hydroxyethyl)piperazine-1-sulfonyl]-2-propoxyphenyl}-1-methyl-3-propyl-1,6-dihydropyrazolo[4,3-d]pyrimidine-7-one；5-[2-ethoxy-5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonylphenyl]-1-methyl-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-7-one；PP-HHS；propoxyphenyl homohydroxysildenafil；5-{5-[4-(2-hydroxyethyl)-1-piperazinylsulphonyl]-2-n-propoxyphenyl}-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one；5-{5-[4-(2-Hydroxyethyl)piperazinylsulphonyl]-2-n-propoxyphenyl}-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one；lodenafil；Propoxyphenyl homohydroxysildenafil；5-[5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonyl-2-propoxyphenyl]-1-methyl-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-7-one
• CAS: 139755-87-6
• 化学式: C₂₄H₃₄N₆O₅S
• 分子量: 518.637
• InChiKey: DDQVAJSWFPJSGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one 、 5-{5-[4-(2-hydroxyethyl)piperazinylsulfonyl]-2-n-propoxyphenyl}-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one 生成 hydroxyhomosildenafil
  参考文献：
  名称：

  Intermediates useful in the synthesis of pyrazolopyrimidinone

  摘要：

  化合物的公式为##STR1##其中R.sup.1是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是H，C.sub.1-C.sub.6烷基，可选择性地被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，或者C.sub.1-C.sub.3全氟烷基；R.sup.3是H，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；Y是氯，溴或氟。上述化合物是合成某些嘧啶并嘧啶酮的中间体，这些嘧啶并嘧啶酮可以抑制环鸟苷3'，5'-单磷酸酯酶。

  公开号：

  US05719283A1
• 作为产物：
  描述：

  N-羟乙基哌嗪 、 5-(5-chlorosulphonyl-2-n-propoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one 以66%的产率得到5-{5-[4-(2-hydroxyethyl)piperazinylsulfonyl]-2-n-propoxyphenyl}-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
  参考文献：
  名称：

  Method of treating a patient having precancerous lesions with phenyl purinone derivatives

  摘要：

  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。

  公开号：

  US06200980B1

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。
• 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。
• Phosphodiesterase type 5 (PDE5) inhibitors for the treatment of selective serotonin reuptake inhibitor (SSR) induced sexual dysfunction
  申请人：——

  公开号：US20030055070A1

  公开（公告）日：2003-03-20

  This invention is directed to the use phosphodiesterase type 5 (PDE5) inhibitors in the treatment of selective serotonin reuptake inhibitor (SSRI) induced sexual dysfunction. Specifically, this invention is directed to a method for treating an animal to cure; prevent or ameliorate SSRI induced sexual dysfunction which comprises administering to the animal an effective amount of the inhibitor. The animal may be a male or a female human. The invention also includes the use of such inhibitors in the manufacture of a medicament to prevent; cure or ameliorate SSRI induced sexual dysfunction. Moreover, the invention includes a kit comprising a SSRI, such as sertraline, fluoxetine, paroxetine, and a PDE5 inhibitor, such as sildenafil citrate, for the treatment or prevention of serotonergic associated disorders such as depression, obsessive compulsive disorder or panic disorder, while reducing or preventing sexual dysfunction.

  该发明涉及使用磷酸二酯酶-5（PDE5）抑制剂治疗选择性血清素再摄取抑制剂（SSRI）引起的性功能障碍。具体而言，该发明涉及一种治疗动物以治愈、预防或改善SSRI引起的性功能障碍的方法，包括向动物施用有效量的抑制剂。该动物可以是男性或女性人类。该发明还包括将这些抑制剂用于制造药物以预防、治愈或改善SSRI引起的性功能障碍。此外，该发明还包括一种套装，其中包括SSRI（如舍曲林、氟西汀、帕罗西汀）和PDE5抑制剂（如西地那非）用于治疗或预防血清素相关疾病，如抑郁症、强迫症或惊恐症，同时减少或预防性功能障碍。
• Methods and compositions for treating diseases and conditions of the eye
  申请人：——

  公开号：US20020119974A1

  公开（公告）日：2002-08-29

  Methods for the prevention and treatment of diseases and conditions of the eye including, but are not limited to: central retinal artery occlusion; central retinal vein occlusion; optic neuropathy including, but not limited to, anterior ischemic optic neuropathy and glaucomatous optic neuropathy; and macular (dry) degeneration are disclosed. These methods comprise administering to a patient a prophylactically or therapeutically effective amount of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase type 5 inhibitor. Pharmaceutical compositions and dosage forms comprising cyclic guanosine 3′,5′-monophosphate phosphodiesterase type 5 inhibitors are also disclosed.

  披露了预防和治疗眼部疾病和病况的方法，包括但不限于：中央视网膜动脉阻塞；中央视网膜静脉阻塞；视神经病变，包括但不限于前部缺血性视神经病变和青光眼性视神经病变；以及黄斑（干性）变性。这些方法包括向患者投予预防性或治疗性有效量的环鸟苷3′,5′-单磷酸磷酸二酯酶类型5抑制剂。还披露了含有环鸟苷3′,5′-单磷酸磷酸二酯酶类型5抑制剂的药物组合物和剂型。
• [EN] PYRAZOLOPYRIMIDINONES FOR THE TREATMENT OF IMPOTENCE<br/>[FR] PYRAZOLOPYRIMIDINONES UTILISEES POUR TRAITER L'IMPUISSANCE
  申请人：PFIZER LIMITED

  公开号：WO1994028902A1

  公开（公告）日：1994-12-22

  (EN) The use of a compound of formula (I) wherein R1 is H; C1-C3 alkyl; C1-C3 perfluoroalkyl; or C3-C5 cycloalkyl; R2 is H; optionally substituted C1-C6 alkyl; C1-C3 perfluoroalkyl; or C3-C6 cycloalkyl; R3 is optionally substituted C1-C6 alkyl; C1-C6 perfluoroalkyl; C3-C5 cycloalkyl; C3-C6 alkenyl; or C3-C6 alkynyl; R4 is optionally substituted C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkanoyl, (hydroxy)C2-C4 alkyl or (C2-C3 alkoxy)C1-C2 alkyl; CONR5R6; CO2R7; halo; NR5R6; NHSO2NR5R6; NHSO2R8; SO2NR9R10; or phenyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, thiazolyl, thienyl or triazolyl any of which is optionally substituted with methyl; R5 and R6 are each independently H or C1-C4 alkyl, or together with the nitrogen atom to which they are attached form an optionally substituted pyrrolidinyl, piperidino, morpholino, 4-N(R11)-piperazinyl or imidazolyl group; R7 is H or C1-C4 alkyl; R8 is optionally substituted C1-C3 alkyl; R9 and R10 together with the nitrogen atom to which they are attached form an optionally substituted pyrrolidinyl, piperidino, morpholino or 4-N(R12)-piperazinyl group; R11 is H; optionally substituted C1-C3 alkyl; (hydroxy)C2-C3 alkyl; or C1-C4 alkanoyl; R12 is H; optionally substituted C1-C6 alkyl; CONR13R14; CSNR13R14; or C(NH)NR13R14; and R?13? and R14 are each independently H; C1-C4 alkyl; or substituted C2-C4 alkyl; or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity, for the manufacture of a medicament for the curative or prophylactic treatment of erectile dysfunction in a male animal, including man; a pharmaceutical composition for said treatment; and a method of said treatment of said male animal with said pharmaceutical composition or with said either entity.(FR) Composé de la formule (I) dans laquelle R1 représente H; alkyle C1-C3, perfluoroalkyle C1-C3; ou cycloalkyle C3-C5; R2 représente H; alkyle C1-C6 éventuellement substitué; perfluoroalkyle C1-C3; ou cycloalkyle C3-C6; R3 représente alkyle C1-C6 éventuellement substitué; perfluoroalkyle C1-C6; cycloalkyle C3-C5; alcényle C3-C6; ou alkynyle C3-C6; R4 représente alkyle C1-C4 éventuellement substitué, alcényle C2-C4, alcanoyle C2-C4, (hydroxy)alkyle C2-C4 ou (alcoxy C2-C3) alkyle C1-C2; CONR5R6; CO2R7, halo; NR5R6; NHSO2NR5R6; NHSO2R8; SO2NR9R10; ou phényle, pyridyle, pyrimidinyle, imidazolyle, oxazolyle, thiazolyle, thiényle ou triazolyle, dont n'importe lequel peut éventuellement être substitué par méthyle; R5 et R6 représentent chacun indépendamment H ou alkyle C1-C4, ou forment, avec l'atome d'azote auquel ils sont rattachés, un groupe pyrrolidinyle, pipéridino, morpholino, 4-N(R11)-pipérazinyle ou imidazolyle éventuellement substitué; R7 représente H ou alkyle C1-C4; R8 représente alkyle C1-C3 éventuellement substitué; R9 et R10 forment, avec l'atome d'azote auquel ils sont rattachés, un groupe pyrrolidinyle, pipéridino, morpholino ou 4-N(R12)pipérazinyle éventuellement substitué; R11 représente H; alkyle C1-C3 éventuellement substitué; (hydroxy)alkyle C2-C3; ou alcanoyle C1-C4; R12 représente H; alkyle C1-C6 éventuellement substitué; CONR13R14; CSNR13R14; ou C(NH)NR3R14; et R13 et R14 représentent chacun indépendamment H; alkyle C1-C4; alkyle C2-C4 substitué. Ce composé, ou un sel pharmaceutiquement acceptable du composé ou une composition pharmaceutique contenant l'un ou l'autre, est utilisé pour la préparation d'un médicament destiné au traitement ou à la prophylaxie d'une absence d'éréction chez un animal mâle, y compris l'homme. Une composition pharmaceutique destinée à ce traitement est également décrite, aisni qu'un procédé de traitement d'un animal mâle au moyen de ladite composition, du composé ou du sel du composé.

  使用公式（I）的化合物，其中R1为H; C1-C3烷基; C1-C3全氟烷基; 或C3-C5环烷基; R2为H; 可选取代的C1-C6烷基; C1-C3全氟烷基; 或C3-C6环烷基; R3为可选取代的C1-C6烷基; C1-C6全氟烷基; C3-C5环烷基; C3-C6烯基; 或C3-C6炔基; R4为可选取代的C1-C4烷基，C2-C4烯基，C2-C4酰基，（羟基）C2-C4烷基或（C2-C3烷氧基）C1-C2烷基; CONR5R6; CO2R7; 卤素; NR5R6; NHSO2NR5R6; NHSO2R8; SO2NR9R10; 或苯基，吡啶基，嘧啶基，咪唑基，噁唑基，噻唑基或三唑基，其中任何一种均可选用甲基取代; R5和R6各自独立地为H或C1-C4烷基，或与它们所连接的氮原子一起形成可选取代的吡咯烷基，哌啶基，吗啉基，4-N（R11）-哌嗪基或咪唑基; R7为H或C1-C4烷基; R8为可选取代的C1-C3烷基; R9和R10与它们所连接的氮原子一起形成可选取代的吡咯烷基，哌啶基，吗啉基或4-N（R12）-哌嗪基; R11为H; 可选取代的C1-C3烷基; （羟基）C2-C3烷基; 或C1-C4酰基; R12为H; 可选取代的C1-C6烷基; CONR13R14; CSNR13R14; 或C（NH）NR13R14; R13和R14各自独立地为H; C1-C4烷基; 或取代的C2-C4烷基; 或其药学上可接受的盐，或包含任一实体的制药组合物，用于制造用于治疗或预防雄性动物，包括人类的勃起功能障碍的药物; 用于该治疗的制药组合物; 以及用该制药组合物或任何实体治疗该雄性动物的方法。