(2R,3R)-2-(2,4-Difluorophenyl)-3-(N-methylamino)-1-(1H-1,2,4-triazol-1-yl)-2-butanol | 138971-00-3

• 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: (2R,3R)-2-(2,4-Difluorophenyl)-3-(N-methylamino)-1-(1H-1,2,4-triazol-1-yl)-2-butanol
• 英文别名: (2R,3R)-2-(2,4-difluorophenyl)-3-(methylamino)-1-(1,2,4-triazol-1-yl)butan-2-ol
• CAS: 138971-00-3
• 化学式: C₁₃H₁₆F₂N₄O
• 分子量: 282.293
• InChiKey: QNTCOBPAHSTWST-NOZJJQNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  63
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2E)-3-(4-氯苯基)丙烯酰氯 、 (2R,3R)-2-(2,4-Difluorophenyl)-3-(N-methylamino)-1-(1H-1,2,4-triazol-1-yl)-2-butanol 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以61%的产率得到(E)-3-(4-Chloro-phenyl)-N-[(1S,2S)-2-(2,4-difluoro-phenyl)-2-hydroxy-1-methyl-3-[1,2,4]triazol-1-yl-propyl]-N-methyl-acrylamide
  参考文献：
  名称：

  Triazole Antifungals. IV. Synthesis and Antifungal Activities of 3-Acylamino-2-aryl-2-butanol Derivatives.

  摘要：

  新设计的并已合成出的三唑类化合物，作为潜在的真菌细胞色素P-450 14α脱甲基酶抑制剂。在对小鼠系统性白色念珠菌感染的抗真菌活性测试中，(2R，3R)-3-酰氨基-2-芳酰基-2-丁醇衍生物III 表现出口服或非肠道给药后的显著高效性。同时，对这些酰氨基醇的构效关系进行了评估。

  DOI：

  10.1248/cpb.39.2581
• 作为产物：
  描述：

  (4R,5R)-5-(2,4-Difluorophenyl)-4-methyl-5-<(1H-1,2,4-triazol-1-yl)methyl>oxazolidine 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以95%的产率得到(2R,3R)-2-(2,4-Difluorophenyl)-3-(N-methylamino)-1-(1H-1,2,4-triazol-1-yl)-2-butanol
  参考文献：
  名称：

  Triazole Antifungals. IV. Synthesis and Antifungal Activities of 3-Acylamino-2-aryl-2-butanol Derivatives.

  摘要：

  新设计的并已合成出的三唑类化合物，作为潜在的真菌细胞色素P-450 14α脱甲基酶抑制剂。在对小鼠系统性白色念珠菌感染的抗真菌活性测试中，(2R，3R)-3-酰氨基-2-芳酰基-2-丁醇衍生物III 表现出口服或非肠道给药后的显著高效性。同时，对这些酰氨基醇的构效关系进行了评估。

  DOI：

  10.1248/cpb.39.2581

文献信息

• Triazole derivatives, their preparation and their use as fungicides
  申请人：Sankyo Company Limited

  公开号：EP0332387A1

  公开（公告）日：1989-09-13

  Compounds of formula (I): in which: Ar is optionally substituted phenyl; R1 is hydrogen or alkyl; X is optionally unsaturated alkylene, cycloalkylene or both; m is 0 or 1; -Yn-R2 is .azido, phthalimido, 1-oxo-2,3-dihy- dro-2-isoindolyl, protected hydroxy or -OS02R4 (in which R4 is alkyl group, haloalkyl or optionally substituted phenyl); or Y represents a group of formula -N(R5)CO-, -N(R5)CO-CH= CH-, -O-CO-, -O-CO-CH = CH-, -S-CO- or -S-CO-CH = CH- (in which R5 is hydrogen or alkyl); n is 0 or 1; R2 is alkyl, haloalkyl or optionally substituted phenyl, naphthyl or heterocyelic; and R3 is hydrogen; or R3 and -Xm-Yn,-R2 together are a group of formula (II): in which R2 is as defined above, p is 0 or 1, and q is 0 or 1; and acid addition salts thereof are fungicides, which find considerable value in the eradication of fungi in both agriculture and medicine.

  式(I)化合物： 其中Ar 是任选取代的苯基；R1 是氢或烷基；X 是任选不饱和亚烷基、环烷基或两者；m 是 0 或 1；-Yn-R2 是.叠氮基、邻苯二甲酰亚胺基、1-氧代-2,3-二氢-2-异吲哚基、受保护羟基或-OS02R4（其中 R4 为烷基、卤代烷基或任选取代的苯基）；或 Y 代表式-N(R5)CO-、-N(R5)CO-CH= CH-、-O-CO-、-O-CO-CH = CH-、-S-CO-或-S-CO-CH = CH-（其中 R5 为氢或烷基）的基团；n 是 0 或 1；R2 是烷基、卤代烷基或任选取代的苯基、萘基或杂环烷基；R3 是氢；或 R3 和 -Xm-Yn,-R2 合在一起是式 (II) 的基团： 其中 R2 如上定义，p 为 0 或 1，q 为 0 或 1；它们的酸加成盐是杀真菌剂，在农业和医药领域根除真菌方面具有相当大的价值。
• Azole compounds, their production and use
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP0510700A2

  公开（公告）日：1992-10-28

  An azole compound represented by the formula (I): wherein X is a nitrogen atom or CH; Ar is a substituted phenyl group; R¹ and R² independently are a hydrogen atom or a lower alkyl group, or they may combine together to form a lower alkylene group; B is a group of the formula: (wherein R³ and R⁴ independently are a hydrogen atom, an optionally substituted aliphatic or aromatic hydrocarbon residue or an optionally substituted heterocyclic group, or they may form an optionally substituted heterocyclic group together with the nitrogen atom to which they are bonded; and n denotes an integer of 0 to 2), or a group of the formula: (wherein R⁵ and R⁶ independently are a hydrogen atom, an optionally substituted aliphatic or aromatic hydrocarbon residue group or an optionally substituted heterocyclic group, or they may form an optionally substituted heterocyclic group together with the nitrogen atom and sulfur atom to which they are bonded; and m denotes an integer of 0 to 2); and R⁷ is a hydrogen atom or an acylated hydroxyl group, or may form a bond together with R¹, or a salt thereof, which is useful as an antifungal agent.

  由式 (I) 代表的唑类化合物： 其中 X 是氮原子或 CH；Ar 是取代的苯基；R¹ 和 R² 分别是氢原子或低级烷基，或它们可结合在一起形成低级亚烷基；B 是式中的一个基团： (其中 R³ 和 R⁴ 各自为氢原子、任选取代的脂肪族或芳香族烃残基或任选取代的杂环基团，或它们可与所键合的氮原子一起形成任选取代的杂环基团；且 n 表示 0 至 2 的整数），或为式中的基团： (其中 R⁵ 和 R⁶ 独立地为氢原子、任选取代的脂肪族或芳香族烃残基或任选取代的杂环基团，或它们可与所键合的氮原子和硫原子一起形成任选取代的杂环基团；R⁷是氢原子或酰化羟基，或可与 R¹ 或其盐一起形成键，可用作抗真菌剂。
• New Azole Antifungals. 2. Synthesis and Antifungal Activity of Heterocyclecarboxamide Derivatives of 3-Amino-2-aryl-1-azolyl-2-butanol
  作者：Javier Bartroli、Enric Turmo、Mònica Algueró、Eulàlia Boncompte、Maria L. Vericat、Lourdes Conte、Joaquim Ramis、Manuel Merlos、Julián García-Rafanell、Javier Forn

  DOI：10.1021/jm970726e

  日期：1998.5.1

  A series of 92 azole antifungals containing an amido alcohol unit was synthesized. The nature and substitution of the amide portion was systematically modified in search of improved antifungal activity, especially against filamentous fungi. The compounds were tested in vitro against a variety of clinically important pathogens and in vivo (po) in a murine candidosis model. Thiazole and thiophene carboxamides carrying both a substituted phenyl ring and a small alkyl. group were best suited for activity against filamentous fungi. In a subset of these compounds, the amide portion was conformationally locked by means of a pyrimidone ring and it was proven that only an orthogonal orientation of the phenyl ring yields bioactive products. A tendency to display long plasma elimination half-lives was observed in both series. Two compounds, 74 and 107, representative of the open and cyclic amides, respectively, were chosen for further studies, based on their excellent activity in in vivo murine models of candidosis and aspergillosis. This work describes the SARs found within this series. The next paper displays the results obtained in a related series of compounds, the quinazolinones.
• NEW CARBOXAMIDES WITH ANTIFUNGAL ACTIVITY
  申请人：J. URIACH & CIA. S.A.

  公开号：EP0783502A1

  公开（公告）日：1997-07-16
• US5360813A
  申请人：——

  公开号：US5360813A

  公开（公告）日：1994-11-01