(2S)-cis-1-[[2-(bromomethyl)-4-(2,4-difluorophenyl)-1,3-dioxolan-4-yl]methyl]-1H-1,2,4-triazole | 219923-97-4

• 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: (2S)-cis-1-[[2-(bromomethyl)-4-(2,4-difluorophenyl)-1,3-dioxolan-4-yl]methyl]-1H-1,2,4-triazole
• 英文别名: 1-[[(2S,4R)-2-(bromomethyl)-4-(2,4-difluorophenyl)-1,3-dioxolan-4-yl]methyl]-1,2,4-triazole
• CAS: 219923-97-4
• 化学式: C₁₃H₁₂BrF₂N₃O₂
• 分子量: 360.158
• InChiKey: UBXZMHWPGBSAHF-QWHCGFSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  49.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S)-cis-1-[[2-(bromomethyl)-4-(2,4-difluorophenyl)-1,3-dioxolan-4-yl]methyl]-1H-1,2,4-triazole 、 5-ethyl-1-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-3-propyl-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 6.5h， 以40%的产率得到1-[4-[4-[4-[[(2S,4R)-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-propyl-1,3,5-triazinane-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：

  2'4'-二氟-2-[1-(1H-1,2,4-三唑基)]苯乙酮 在 sodium hydroxide 、 甲烷磺酸 、 硫酸 、 苄基三乙基氯化铵 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 24.0h， 生成 (2S)-cis-1-[[2-(bromomethyl)-4-(2,4-difluorophenyl)-1,3-dioxolan-4-yl]methyl]-1H-1,2,4-triazole
  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

• Method for Manufacture of 2-Oxoimidazolidines
  申请人：Peterson John R.

  公开号：US20100222588A1

  公开（公告）日：2010-09-02

  There is provided a method for manufacture of 2-oxoimidazolidines of Formula I comprising one or more of the steps of converting an amine to an acylation agent, condensation of the acylation agent with a bi-functional compound of structure L-C(R 4 )(R 5 )—C(R 2 )(R 3 )—NHR 1 , wherein L is a leaving group, and ring closure of the resulting urea. In this manner, certain 2-oxoimidazolidines may be manufactured that are useful intermediates for the production of Pramiconazole and structurally related compounds.

  提供了一种制备式I的2-氧代咪唑啉的方法，包括以下一项或多项步骤：将胺转化为酰化剂，将酰化剂与结构为L-C(R4)(R5)—C(R2)(R3)—NHR1的双功能化合物缩合，其中L是一个离去基团，并闭环生成的脲。通过这种方式，可以制备出一些对于生产Pramiconazole和结构相关化合物有用的2-氧代咪唑啉中间体。
• METHOD FOR MANUFACTURE OF 2-OXOIMIDAZOLIDINES
  申请人：Peterson John R.

  公开号：US20130237705A1

  公开（公告）日：2013-09-12

  A method for the manufacture of 2-oxoimidazolidines comprising the steps of converting an isocyanate and an amine to a urea, and then performing a ring closure of the urea to yield the 2-oxoimidazolidine is disclosed. The 2-oxoimidazolidines produced may then be used in the production of Pramiconazole and other structurally related compounds.

  公开了一种制造2-氧代咪唑啉的方法，包括将异氰酸酯和胺转化为尿素，然后进行环闭合反应以产生2-氧代咪唑啉。所生产的2-氧代咪唑啉可以用于生产Pramiconazole和其他结构相关的化合物。
• 2,4,4-Tri- and 2,2,4,4-tetra-substituted-1,3-dioxolane
  申请人：SCHERING CORPORATION

  公开号：EP0278105A1

  公开（公告）日：1988-08-17

  2,4,4-tri- and 2,2,4,4-tetra substituted-1,3-­dioxolane compounds and pharmaceutically acceptable salts and solvates thereof are disclosed which possess anti-­fungal, anti-allergy, anti-inflammatory and/or immuno-­modulation activity. Methods for preparing and using the compounds also are described.

  公开了具有抗真菌、抗过敏、抗炎和/或免疫调节活性的 2,4,4- 三取代和 2,2,4,4- 四取代-1,3-二氧戊环化合物及其药学上可接受的盐和溶液。此外，还描述了制备和使用这些化合物的方法。
• [EN] 2,4,4-TRI- AND 2,2,4,4-TETRA SUBSTITUTED-1,3-DIOXOLANE COMPOUNDS
  申请人：SCHERING CORPORATION

  公开号：WO1988005048A1

  公开（公告）日：1988-07-14

  (EN) 2,4,4-tri- and 2,2,4,4-tetra substituted-1,3-dioxolane compounds and pharmaceutically acceptable salts and solvates thereof which possess anti-fungal, anti-allergy, anti-inflammatory and/or immuno modulation activity. Methods for preparing and using the compounds also are described.(FR) Ces composés et leurs sels et solvats acceptables sur le plan pharmaceutique possèdent des propriétés antimycosiques, antiallergiques, anti-inflammatoires et/ou immunomodulatrices. Les modes de préparation et les utilisations de ces composés sont également décrits.

  2,4,4-三取代和2,2,4,4-四取代-1,3-间二甲基呋喃类化合物及其 pharmaceutically acceptable盐和溶剂，这些化合物具有抗真菌、抗过敏、抗炎及/或免疫调节活性。合成及其应用方式亦被描述。
• SAKSENA, ANIL K.;COOPER, ALAN B.;GUZIK, HENRY;GIRIJAVALLABHAN, VIYOOR M.;+
  作者：SAKSENA, ANIL K.、COOPER, ALAN B.、GUZIK, HENRY、GIRIJAVALLABHAN, VIYOOR M.、+

  DOI：——

  日期：——