trans-1-[[2-(bromomethyl)-4-(2,4-difluorophenyl)-1,3-dioxolan-4-yl]methyl]-1H-1,2,4-triazole

• 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: trans-1-[[2-(bromomethyl)-4-(2,4-difluorophenyl)-1,3-dioxolan-4-yl]methyl]-1H-1,2,4-triazole
• 英文别名: (2R-cis)-1-[[2-(bromomethyl)-4-(2,4-difluorophenyl)-1,3-dioxolan-4-yl]methyl]-1H-1,2,4-triazole；cis-1-[[2-(bromomethyl)-4-(2,4-difluorophenyl)-1,3-dioxolan-4-yl]methyl]-1H-1,2,4-triazole；1-[[2-(Bromomethyl)-4-(2,4-difluorophenyl)-1,3-dioxolan-4-yl]methyl]-1,2,4-triazole
• 化学式: C₁₃H₁₂BrF₂N₃O₂
• 分子量: 360.158
• InChiKey: UBXZMHWPGBSAHF-UHFFFAOYSA-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：

  trans-1-[[2-(bromomethyl)-4-(2,4-difluorophenyl)-1,3-dioxolan-4-yl]methyl]-1H-1,2,4-triazole 、 (+/-)CIS-4-[4-[4-[4-[[4-(2,4-DIFLUOROPHENYL)-4-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-1,3-DIOXOLAN-2-YL]METHOXY]PHENYL]-1-PIPERAZINYL]PHENYL]-2,4-DIHYDRO-2-(1-METHYLPROPYL)-3H-1,2,4-TRIAZOL-3-ONE 、 1-乙酰基-4-(4-羟基苯基)哌嗪 以 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 (+/-)CIS-1-ACETYL-4-[4[[4-(2,4-DIFLUOROPHENYL)-4-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-1,3-DIOXOLAN-2-YL]METHOXY]PHENYL]PIPERAZINE
  参考文献：
  名称：

  2,4,4-tri- and 2,2,4,4-tetra substituted-1,3-dioxolane antifungal,

  摘要：

  新型1,3-二氧杂环戊酮化合物可用作抗真菌和抗过敏剂，其化学式表示为##STR1##其中Ar为噻吩基、吡啶基、联苯基、苯基或苯基，其上取代一个或多个卤素、硝基、氰基、较低烷基、较低烷氧基或全氟较低烷基；Y为CH或N；Q为##STR2##W为--NR.sub.5 --、--O--、--S(O).sub.n --；X为NO.sub.2、NR.sub.6 R.sub.7或COR.sub.8；R.sub.1、R.sub.2、R.sub.3和R.sub.4独立地为氢或较低烷基；R.sub.5为氢、较低烷基或(C.sub.2 -C.sub.6)烷酰基；R.sub.6和R.sub.7独立地为氢、较低烷基、苯基或苯基，其上取代一个或多个卤素、全氟较低烷基、(C.sub.2 -C.sub.6)烷酰基较低烷基、较低烷氧基或2-较低烷基-3-氧代-1,2,4-三唑-4-基或R.sub.6和R.sub.7与NR.sub.6 R.sub.7中的氮原子一起形成取代或未取代的杂环基，所述杂环基取代基为(C.sub.2 -C.sub.6)烷酰基、较低烷基、苯基或苯基，其上取代一个或多个卤素、全氟较低烷基、(C.sub.2 -C.sub.6)烷酰基、较低烷基、较低烷氧基或2-较低烷基-3-氧代-1,2,4-三唑-4-基，R.sub.8为较低烷基、较低烷氧基、--NR.sub.1 R.sub.2、苯基或苯基，其上取代一个或多个卤素、全氟较低烷基、较低烷基、较低烷氧基、硝基、氰基或(C.sub.2 -C.sub.6)烷酰基，p为0、1、2、3、4或5，n为0、1或2，以及它们的立体异构体，可以是消旋体或光学活性形式；或其药学上可接受的盐。

  公开号：

  US04788190A1
• 作为产物：
  描述：

  2'4'-二氟-2-[1-(1H-1,2,4-三唑基)]苯乙酮 在 盐酸 、 ammonium hydroxide 、 lithium aluminium tetrahydride 、 甲烷磺酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 94.0h， 生成 trans-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。
• Watersoluble azole antifungals
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US05707977A1

  公开（公告）日：1998-01-13

  A compound of formula (I), ##STR1## an acid or base addition salt thereof or a stereochemically isomeric form thereof, wherein A and B taken together form --N.dbd.CH--, --CH.dbd.N--, --CH.sub.2 --CH.sub.2, CH.dbd.CH--, --C(.dbd.O)--CH.sub.2 --, --CH.sub.2 --C(.dbd.O); D is a radical of formula ##STR2## L is a radical of formula ##STR3## Alk is a C.sub.1-4 alkanediyl radical; R.sup.1 is halo; R.sup.2 is hydrogen or halo; R.sup.3 is hydrogen, C.sub.1-6 alkyl, phenyl or halophenyl; R.sup.4 is hydrogen, C.sub.1-6 alkyl, phenyl or halophenyl; R.sup.5 is hydrogen or C.sub.1-6 alkyl; R.sup.6 is hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkyloxycarbonyl, or R.sup.5 and R.sup.6 taken together with the nitrogen atom to which they are attached form a heterocyclic ring. Active intermediates, compositions and methods of preparing compounds, compositions are described.

  公式（I）的化合物，##STR1## 其酸盐或碱盐加合物，或其立体化学异构体形式，其中A和B共同形成--N.dbd.CH--, --CH.dbd.N--, --CH.sub.2 --CH.sub.2, CH.dbd.CH--, --C(.dbd.O)--CH.sub.2 --, --CH.sub.2 --C(.dbd.O); D是公式##STR2##的基团；L是公式##STR3##的基团；Alk是C.sub.1-4烷二基基团；R.sup.1是卤素；R.sup.2是氢或卤素；R.sup.3是氢，C.sub.1-6烷基，苯基或卤苯基；R.sup.4是氢，C.sub.1-6烷基，苯基或卤苯基；R.sup.5是氢或C.sub.1-6烷基；R.sup.6是氢，C.sub.1-6烷基，C.sub.1-6烷氧羰基，或R.sup.5和R.sup.6与它们连接的氮原子共同形成一个杂环环。描述了活性中间体、组合物和制备化合物、组合物的方法。
• 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。