3-amino-1-methyl-4-propyl-1H-pyrrole-2-carboxamide | 356044-93-4

• 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
• 英文名称: 3-amino-1-methyl-4-propyl-1H-pyrrole-2-carboxamide
• 英文别名: 4-amino-1-methyl-3-n-propylpyrrole-5-carboxamide；3-Amino-1-methyl-4-propylpyrrole-2-carboxamide
• CAS: 356044-93-4
• 化学式: C₉H₁₅N₃O
• 分子量: 181.238
• InChiKey: YSJRCTVNJBPEKM-UHFFFAOYSA-N

物化性质

• 沸点：
  310.5±42.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  74
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-amino-1-methyl-4-propyl-1H-pyrrole-2-carboxamide 在 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.08h， 生成 5-methyl-2-(2-propoxyphenyl)-7-propyl-3,5-dihydro-4H-pyrrolo[3,2-d]pyrimidin-4-one
  参考文献：
  名称：

  [EN] NOVEL DUAL MODE OF ACTION SOLUBLE GUANYLATE CYCLASE ACTIVATORS AND PHOSPHODIESTERASE INHIBITORS AND USES THEREOF
  [FR] NOUVEAUX ACTIVATEURS DE LA GUANYLATE CYCLASE SOLUBLES À DOUBLE MODE D'ACTION, INHIBITEURS DE PHOSPHODIESTÉRASE ET LEURS UTILISATIONS

  摘要：

  本发明涉及公式I的化合物或其药用可接受的盐、溶剂或水合物，以及它们在治疗或预防通过抑制人类或非人类哺乳动物中的PDE5而缓解的疾病的方法中的应用。

  公开号：

  WO2018215433A1
• 作为产物：
  描述：

  N-(2-cyano-2-n-propylvinyl)-N-methylglycine amide 在 NaOEt 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 以92%的产率得到3-amino-1-methyl-4-propyl-1H-pyrrole-2-carboxamide
  参考文献：
  名称：

  Pyrrolopyrimidinone derivatives, process of preparation and use

  摘要：

  本发明涉及一系列具有式(1)结构的吡咯并嘧啶酮衍生物，其制备方法，制备过程中的中间体，它们作为治疗剂的用途，以及含有它们的药物组合物。

  公开号：

  US20030171361A1

文献信息

• Dual mode of action soluble guanylate cyclase activators and phosphodiesterase inhibitors and uses thereof
  申请人：TOPADUR PHARMA AG

  公开号：US11155558B2

  公开（公告）日：2021-10-26

  The present invention relates to compounds of formula I or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein at least one of R1, R2, R3, R4, or R5 independently of each other comprises at least one ONO2 or ONO moiety; R1 is C1-C3alkyl optionally substituted with F, C3-C6cycloalkyl, C1-C3alkoxy, ONO, ONO2; R2 is H, C1-C3alkyl optionally substituted with OH, ONO, ONO2; C(O)OH, C(O)OC1-C3alkyl, CHO, CN, C(O)N(R6)OR7, CR8═N—OR9, CR8═N—NR10R11, CR8═NR12, CR8═N—ONO2, C1-C3alkoxy; C1-C3alkylene-Y, wherein Y is ONO, ONO2, C(O)OH, C(O)OC1-C3alkyl, CHO, CN, OH, OC(O)H, OC(O)—C1-C3alkyl, C(O)N(R6)OR7, OC1-C3alkylene-C(O)OH, OC1-C3alkylene-C(O)OC1-C3alkyl, OC1-C3alkylene-C(O)N(R6)OR7, S(O0-2)C1-C3alkyl, CR8═N—OR9, CR8═N—NR10R11, CR8═NR12 or CR8═N—ONO2; R3 is C1-C4alkyl optionally substituted with F, OH, ONO, ONO2, C1-C3alkoxy, C3-C6cycloalkyl; C3-C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl; R4 is C1-C6alkyl optionally substituted with C3-C6cycloalkyl, C1-C6alkoxy, F, ONO, ONO2; C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl; R5 is H, SO2NR13R14, NHSO2NR13R14; R6 is H or C1-C3alkyl; R7 is H, C1-C3alkyl, C1-C3alkoxy, C1-C3alkyl substituted with phenyl, benzyl or a heterocyclic ring, wherein said phenyl, benzyl or said heterocyclic ring are independently optionally substituted by C1-C3alkyl, F; R8 is H, CH3 or C2H5; R9 is H, C1-C3alkyl optionally substituted with OH, ONO, ONO2, CN, COOH, COOC1-C3alkyl, C1-C3alkoxy, OC(O)H, OC(O)—C1-C3alkyl, C(O)N(R6)OR7, OC1-C3alkylene-C(O)OH, OC1-C3alkylene-C(O)OC1-C3alkyl, OC1-C3alkylene-C(O)N(R6)OR7, S(O0-2)C1-C3alkyl; R10 and R11 are each independently H, C1-C3alkyl optionally substituted with OH, ONO, ONO2, CN, COOH, COOC1-C3, C1-C3alkoxy, OC(O)H, OC(O)—C1-C3alkyl, C(O)N(R6)OR7, OC1-C3alkylene-C(O)OH, OC1-C3alkylene-C(O)OC1-C3alkyl, OC1-C3alkylene-C(O)N(R6)OR7, S(O0-2)C1-C3alkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine and homopiperazine, wherein said heterocyclic ring is optionally substituted with C1-C3 alkyl; R12 is C1-C3 alkyl optionally substituted with OH, ONO, ONO2, CN, COOH, COOC1-C3alkyl, C1-C3alkoxy, OC(O)H, OC(O)—C1-C3alkyl, C(O)N(R6)OR7, OC1-C3alkylene-C(O)OH, OC1-C3alkylene-C(O)OC1-C3alkyl, OC1-C3alkylene-C(O)N(R6)OR7, S(O0-2)C1-C3alkyl; R13 and R14 are each independently H or C1-C6alkyl optionally substituted with F, OH, ONO, ONO2, COOH, C1-C3alkoxy, C3-C6cycloalkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine, homopiperazine, 2,5-diazabicyclo[2,2,1]heptane and 3,7-diazabicyclo[3,3,0]octane, wherein said heterocyclic ring is optionally substituted with R15; R15 is C1-C6alkyl optionally substituted with halogen, OH, ONO, ONO2, C1-C3alkoxy, C1-C3haloalkoxy, COOR16, NR17R18, C═NR19, or with a tetrazole moiety which is optionally substituted with C1-C3alkyl; or a heteroaryl ring which is optionally substituted with F, wherein the at least one heteroatom of said heteroaryl ring is nitrogen; R16 is H, or C1-C4alkyl optionally substituted with F, OH, ONO, ONO2, NR17R18, or with a heteroaryl ring, wherein the at least one heteroatom of said heteroaryl ring is nitrogen, and wherein preferably said heteroaryl ring is selected from pyrrolidine, piperidine, piperazine, morpholine, pyrrole, and imidazole, wherein nitrogen atom is directly bound to C1-C4 alkyl; R17 and R18 are each independently H or C1-C4alkyl optionally substituted with ONO, ONO2; R19 is C1-C4alkyl optionally substituted with F, ONO, ONO2; C3-C6cycloalkyl; and their use in methods of treating or preventing a disease alleviated by inhibition of PDE5 in a human or in a non-human mammal.

  本发明涉及式 I 的化合物 或其药学上可接受的盐、溶液或水合物，其中 R1、R2、R3、R4 或 R5 中至少有一个相互独立地包含至少一个 ONO2 或 ONO 分子； R1 是任选被 F、C3-C6 环烷基、C1-C3 烷氧基、ONO、ONO2 取代的 C1-C3 烷基； R2 是 H、任选被 OH、ONO、ONO2 取代的 C1-C3 烷基；C(O)OH、C(O)OC1-C3 烷基、CHO、CN、C(O)N(R6)OR7、CR8═N-OR9、CR8═N-NR10R11、CR8═NR12、CR8═N-ONO2、C1-C3 烷氧基；C1-C3 烷基-Y，其中 Y 是 ONO、ONO2、C(O)OH、C(O)OC1-C3 烷基、CHO、CN、OH、OC(O)H、OC(O)-C1-C3 烷基、C(O)N(R6)OR7、OC1-C3 烷基-C(O)OH、OC1-C3烷基-C(O)OC1-C3烷基、OC1-C3烷基-C(O)N(R6)OR7、S(O0-2)C1-C3烷基、CR8═N-OR9、CR8═N-NR10R11、CR8═NR12 或 CR8═N-ONO2； R3 是任选被 F、OH、ONO、ONO2、C1-C3 烷氧基、C3-C6 环烷基、C3-C6 环烷基、C2-C6 烯基、C2-C6炔基取代的 C1-C4 烷基； R4 是被 C3-C6环烷基、C1-C6烷氧基、F、ONO、ONO2、C2-C6烯基、C2-C6炔基、C3-C6环烷基任选取代的 C1-C6 烷基； R5 是 H、SO2NR13R14、NHSO2NR13R14； R6 是 H 或 C1-C3 烷基 R7 是 H、C1-C3烷基、C1-C3烷氧基、被苯基、苄基或杂环取代的 C1-C3烷基，其中所述苯基、苄基或所述杂环独立地任选被 C1-C3烷基、F 取代； R8 是 H、CH3 或 C2H5； R9 是 H、任选被 OH、ONO、ONO2、CN、COOH、COOC1-C3 烷基、C1-C3 烷氧基、OC(O)H、OC(O)-C1-C3 烷基、C(O)N(R6)OR7、OC1-C3 亚烷基-C(O)OH、OC1-C3 亚烷基-C(O)OC1-C3 烷基、OC1-C3 亚烷基-C(O)N(R6)OR7、S(O0-2)C1-C3 烷基取代的 C1-C3 烷基； R10和R11各自独立地为H、被OH、ONO、ONO2、CN、COOH、COOC1-C3、C1-C3烷氧基、OC(O)H、OC(O)-C1-C3烷基、C(O)N(R6)OR7、OC1-C3亚烷基-C(O)OH、OC1-C3亚烷基-C(O)OC1-C3烷基、OC1-C3亚烷基-C(O)N(R6)OR7、S(O0-2)C1-C3烷基任选取代的C1-C3烷基；或与所连接的氮原子一起形成杂环，其中优选所述杂环选自氮丙啶、氮杂环丁烷、吡咯烷、哌啶、吗啉、哌嗪和均哌嗪，其中所述杂环任选被 C1-C3 烷基取代； R12 是任选被 OH、ONO、ONO2、CN、COOH、COOC1-C3 烷基、C1-C3 烷氧基、OC(O)H、OC(O)-C1-C3 烷基、C(O)N(R6)OR7、OC1-C3 亚烷基-C(O)OH、OC1-C3 亚烷基-C(O)OC1-C3 烷基、OC1-C3 亚烷基-C(O)N(R6)OR7、S(O0-2)C1-C3 烷基取代的 C1-C3 烷基； R13 和 R14 各自独立地为 H 或被 F、OH、ONO、ONO2、COOH、C1-C3 烷氧基、C3-C6 环烷基任选取代的 C1-C6 烷基；或与所连接的氮原子一起形成杂环，其中优选所述杂环选自氮丙啶、氮杂环丁烷、吡咯烷、哌啶、吗啉、哌嗪、均哌嗪、2,5-二氮杂双环[2,2,1]庚烷和 3,7-二氮杂双环[3,3,0]辛烷，其中所述杂环任选被 R15 取代； R15 是被卤素、OH、ONO、ONO2、C1-C3 烷氧基、C1-C3 卤烷氧基、COOR16、NR17R18、C═NR19 或被 C1-C3 烷基任选取代的四唑分子任选取代的 C1-C6 烷基；或被 F 任选取代的杂芳基环，其中所述杂芳基环的至少一个杂原子是氮； R16 是 H，或被 F、OH、ONO、ONO2、NR17R18 或杂芳基环任选取代的 C1-C4 烷基，其中所述杂芳基环的至少一个杂原子是氮，优选所述杂芳基环选自吡咯烷、哌啶、哌嗪、吗啉、吡咯和咪唑，其中氮原子直接与 C1-C4 烷基结合； R19是任选被F、ONO、ONO2取代的C1-C4烷基；C3-C6环烷基； 以及它们在治疗或预防通过抑制人或非人哺乳动物中的 PDE5 而减轻的疾病的方法中的用途。
• PYRROLOPYRIMIDINONE DERIVATIVES, PROCESS OF PREPARATION AND USE
  申请人：SK Chemicals Co., Ltd.

  公开号：EP1257553B1

  公开（公告）日：2004-05-26
• NOVEL DUAL MODE OF ACTION SOLUBLE GUANYLATE CYCLASE ACTIVATORS AND PHOSPHODIESTERASE INHIBITORS AND USES THEREOF
  申请人：Topadur Pharma AG

  公开号：EP3630769A1

  公开（公告）日：2020-04-08
• DUAL MODE OF ACTION SOLUBLE GUANYLATE CYCLASE ACTIVATORS AND PHOSPHODIESTERASE INHIBITORS AND USES THEREOF
  申请人：TOPADUR PHARMA AG

  公开号：US20220073529A1

  公开（公告）日：2022-03-10

  The present invention relates to compounds of formula I or pharmaceutically acceptable salt, solvate or hydrate thereof and their use in methods of treating or preventing a disease alleviated by inhibition of PDE5 in a human or in a non-human mammal.
• US6962911B2
  申请人：——

  公开号：US6962911B2

  公开（公告）日：2005-11-08