1-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-5,5-dimethyl-2,4,6(1H,3H,5H)-pyrimidinetrione | 219923-99-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-5,5-dimethyl-2,4,6(1H,3H,5H)-pyrimidinetrione
• 英文别名: 1-[4-[4-(4-methoxyphenyl)-1-piperazinyl)phenyl]-5,5-dimethyl-2,4,6(1H,3H,5H)-pyrimidinetrione；1-[4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]-5,5-dimethyl-1,3-diazinane-2,4,6-trione
• CAS: 219923-99-6
• 化学式: C₂₃H₂₆N₄O₄
• 分子量: 422.484
• InChiKey: LZVNNGAVEXZKKL-UHFFFAOYSA-N

物化性质

• 密度：
  1.253±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-5,5-dimethyl-2,4,6(1H,3H,5H)-pyrimidinetrione 在 氢溴酸 、 sodium hexamethyldisilazane 、 sodium hydride 、 sodium hydrogensulfite 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 1-[4-[4-[4-[[(2R,4S)-4-(2,4-difluorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-3-ethyl-5,5-dimethyl-1,3-diazinane-2,4,6-trione
  参考文献：
  名称：

  Synthesis and in Vitro and in Vivo Structure−Activity Relationships of Novel Antifungal Triazoles for Dermatology

  摘要：

  In search for new compounds with potential for clinical use as antifungal agents in dermatology, a series of 12 azole compounds were synthesized stereospecifically and investigated specifically for their activity against dermatophyte fungal infections in animal models. This panel of azoles was studied in vitro and compared with itraconazole and terbinafine for their antifungal activity using a panel of 24 Candida spp. and 182 dermatophyte isolates. Three azoles (1c, 2c, and 4c) showed in vitro antifungal potency equivalent to itraconazole, but superior to terbinafine, against a panel of 24 Candida spp. with comparable or lower activity than that of itraconazole and terbinafine against 182 dermatophyte isolates and only rare activity against other pathogenic fungi. However, in vivo 1c and 4c, both given orally, demonstrated antifungal activity at least three times greater than itraconazole and were superior compared to terbinafine in M. cants infected guinea pigs. In a mouse model infected by T mentagrophytes, again 4c, but not 1c, showed 5-fold superior activity over itraconazole and terbinafine. Compound 2c was effective in both models but less effective than itraconazole in these models. On the basis of these promising results, 4c is currently being clinically investigated for its potential as a novel antifungal agent against dermatophytosis.

  DOI：

  10.1021/jm0494772
• 作为产物：
  描述：

  1-(4-氨基苯基)-4-(4-甲氧基苯基)哌嗪 在 盐酸 作用下， 以 环丁砜 为溶剂， 反应 9.0h， 生成 1-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-5,5-dimethyl-2,4,6(1H,3H,5H)-pyrimidinetrione
  参考文献：
  名称：

  Synthesis and in Vitro and in Vivo Structure−Activity Relationships of Novel Antifungal Triazoles for Dermatology

  摘要：

  In search for new compounds with potential for clinical use as antifungal agents in dermatology, a series of 12 azole compounds were synthesized stereospecifically and investigated specifically for their activity against dermatophyte fungal infections in animal models. This panel of azoles was studied in vitro and compared with itraconazole and terbinafine for their antifungal activity using a panel of 24 Candida spp. and 182 dermatophyte isolates. Three azoles (1c, 2c, and 4c) showed in vitro antifungal potency equivalent to itraconazole, but superior to terbinafine, against a panel of 24 Candida spp. with comparable or lower activity than that of itraconazole and terbinafine against 182 dermatophyte isolates and only rare activity against other pathogenic fungi. However, in vivo 1c and 4c, both given orally, demonstrated antifungal activity at least three times greater than itraconazole and were superior compared to terbinafine in M. cants infected guinea pigs. In a mouse model infected by T mentagrophytes, again 4c, but not 1c, showed 5-fold superior activity over itraconazole and terbinafine. Compound 2c was effective in both models but less effective than itraconazole in these models. On the basis of these promising results, 4c is currently being clinically investigated for its potential as a novel antifungal agent against dermatophytosis.

  DOI：

  10.1021/jm0494772

文献信息

• 2,4,4-trisubstituted-1,3-dioxolane antifungals
  申请人：——

  公开号：US06387906B1

  公开（公告）日：2002-05-14

  The present invention concerns novel compounds of formula a N-oxide form, a pharmaceutically acceptable acid addition salt or a stereochemically isomeric form thereof, wherein n is zero, 1, 2 or 3; X is N or CH; each R1 independently is halo, nitro, cyano, amino, hydroxy, C1-4alkyl, C1-4alkyloxy or trifluoromethyl; R2 is hydrogen; C3-7alkenyl; C3-7alkynyl, aryl; C3-7cycloalkyl; optionally substituted C1-6alkyl R3 and R4 each independently are hydrogen, C1-6alkyl, C3-7cycloalkyl or aryl; or R3 and R4 taken together form a bivalent radical —R3—R4— of formula: wherein R5a, R5b, R5c, R5d each independently are hydrogen, C1-6alkyl or aryl; and aryl is optionally substituted phenyl; as antifungals; their preparation, compositions containing them and their use as a medicine.

  本发明涉及公式a的新化合物的N-氧化物形式，药学上可接受的酸盐或其立体化异构形式，其中n为零、1、2或3；X为N或CH；每个R1独立地为卤素、硝基、氰基、氨基、羟基、C1-4烷基、C1-4烷氧基或三氟甲基；R2为氢；C3-7烯基；C3-7炔基、芳基；C3-7环烷基；可选择取代的C1-6烷基R3和R4各自独立地为氢、C1-6烷基、C3-7环烷基或芳基；或R3和R4一起形成一个二价基团-R3-R4-的公式：其中R5a、R5b、R5c、R5d各自独立地为氢、C1-6烷基或芳基；芳基为可选择取代的苯基；作为抗真菌剂；它们的制备、含有它们的组合物以及它们作为药物的用途。
• 2,4,4-TRISUBSTITUTED-1,3-DIOXOLANE ANTIFUNGALS
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1068200B1

  公开（公告）日：2005-02-16
• US6387906B1
  申请人：——

  公开号：US6387906B1

  公开（公告）日：2002-05-14