(2R,3R)-3-Amino-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol | 127181-91-3

• 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)-3-Amino-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol
• 英文别名: (2R*,3R*)-3-amino-1-(1H-1,2,4-triazol-1-yl)-2-(2,4-dichlorophenyl)-2-butanol；(2R,3R)-3-amino-2-(2,4-dichlorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-ol
• CAS: 127181-91-3
• 化学式: C₁₂H₁₄Cl₂N₄O
• 分子量: 301.175
• InChiKey: LDFDJOAYWXMRKU-PRHODGIISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  77
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R,3R)-3-Amino-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol 在 palladium on activated charcoal lithium aluminium tetrahydride 、 TEA 、 氢气 、 二甲基亚砜 、 三乙胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 甲苯 为溶剂， -78.0~25.0 ℃ 、101.33 kPa 条件下， 反应 103.0h， 生成 (2S^*,5R^*,6R^*)-6-(2,4-dichlorophenyl)-5-methyl-2-hydroxy-4-<4-(trifluoromethyl)benzoyl>-6-<(1H-1,2,4-triazol-1-yl)methyl>morpholine
  参考文献：
  名称：

  Synthesis and Antifungal Activity of New Azole Derivatives Containing an N-Acylmorpholine Ring

  摘要：

  A series of azole derivatives carrying an N-acylmorpholine ring are described. The compounds were chemically designed to simulate the lanosterol D ring, taking advantage of the conformational preferences of 2-alkyl-1-acylmorpholines. Three structural variables, the nature of the N-benzoyl group, the phenyl substituents, and the degree of oxidation at carbon 2 of the morpholine, were optimized for maximum activity. Only the (5R,6R) isomers showed antifungal activity. Cyclic hemiacetal(-)-39a (UR-9746) and cyclic ether (-)-41 (UR-9751) were selected for further development. In vitro, (-)-41 was clearly more active than (-)-39a and somewhat less active than the acyclic counterpart (-)-7. lit vivo activity was assessed by a systemic (mouse) and a vaginal (rat) candidosis model. In the former, (-)-39a, (-)-41, and (-)-7 at 1 mg/kg given 1, 4, and 24 h postinfection displayed 90-100% protection from mortality on day 9. Compound (-)-39a was slightly more potent than (-)-41 and similar in potency to (-)-7. The three compounds were superior in potency to fluconazole and similar in potency to SCH-42427 in this test. In the vaginal model, (-)-39a and (-)-41 given daily during 3 days after infection at 0.5 mg/kg showed high levels of protection on days 10 and 15. At 0.25 mg/kg, (-)-39a was slightly more potent than SCH-42427 and (-)-7 and superior in potency to (-)-41 and fluconazole in this model. Preliminary 28-day toxicity tests at 100 mg/kg/day po in rats indicated no or very mild adverse effects for the two UR compounds.

  DOI：

  10.1021/jm00020a005
• 作为产物：
  描述：

  (2S,3S)-3-azido-2-(2,4-dichlorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-ol 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以100%的产率得到(2R,3R)-3-Amino-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol
  参考文献：
  名称：

  三唑类抗真菌药。二。3-酰基-4-甲基恶唑烷衍生物的合成和抗真菌活性。

  摘要：

  设计并合成了具有恶唑烷环的三唑化合物，作为真菌细胞色素P450 14α-脱甲基酶的潜在抑制剂。在针对小鼠全身性白色念珠菌感染的抗真菌活性测试中，口服或肠胃外给药后，（4R，5R）-3-酰基-4-甲基恶唑烷衍生物4表现出显着的高功效。假设4的有效活性是4与羊毛甾醇（细胞色素P450 14α-脱甲基酶的靶分子）之间的结构相似性的结果。还描述了这些恶唑烷的高度立体选择性合成。

  DOI：

  10.1248/cpb.38.2476

文献信息

• Triazole Antifungals. IV. Synthesis and Antifungal Activities of 3-Acylamino-2-aryl-2-butanol Derivatives.
  作者：Toshiyuki KONOSU、Yawara TAJIMA、Noriko TAKEDA、Takeo MIYAOKA、Mayumi KASAHARA、Hiroshi YASUDA、Sadao OIDA

  DOI：10.1248/cpb.39.2581

  日期：——

  New triazole compounds were designed and synthesized as potential inhibitors of the fungal cytochrome P-450 14α-demethylase. In testing for antifungal activity against a mouse systemic Candida albicans infection, (2R, 3R)-3-acylamino-2-aroyl-2-butanol derivatives III exhibited remarkably high efficacy after oral or parenteral administration. The structure-activity relationships of these amidoalcohols were evaluated.

  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。
• Pyrimidone derivatives with antifungal activity
  申请人：J. Uriah & Cia. S.A.

  公开号：US05807854A1

  公开（公告）日：1998-09-15

  Compounds of general formula I and their salts and solvates are antifungal agents and as such are useful in the treatment of various fungal infections. Pharmaceutical compositions including these compounds and processes for their preparation are also provided.

  通式I的化合物及其盐和溶剂合物是抗真菌剂，因此在治疗各种真菌感染方面非常有用。还提供包括这些化合物的药物组合物和其制备方法。
• Orally active azole derivatives
  申请人：J. Uriach & Cia. S.A.

  公开号：US05478826A1

  公开（公告）日：1995-12-26

  The present invention relates to new orally active azole derivatives with antifungal activity of formula I ##STR1## wherein: X is CH or N; Ar represents phenyl substituted with halogen and/or trifluoromethyl; Z is --C(=O)-- or --SO.sub.2 --; R.sub.1 is CN, CO.sub.2 H, CO.sub.2 R.sub.7, CONR.sub.8 R.sub.9 or CH.sub.2 Y and then R.sub.3 is hydrogen, or R.sub.1 together with R.sub.3 forms a ring of formula I' ##STR2## wherein B is O, hydroxy or hydrogen; R.sub.4 is C.sub.1-4 alkyl; R.sub.5, R.sub.6, R.sub.8 and R.sub.9 are hydrogen or C.sub.1-4 alkyl; Y is --OH, --OR.sub.7, --OC(=O)R.sub.7, --NR.sub.8 R.sub.9, --NHC(=O)OR.sub.7 ; R.sub.7 is C.sub.1 -C.sub.4 -alkyl, phenyl-C.sub.1 -C.sub.4 -alkyl or optionally substituted phenyl; when Z is --C(=O)--, R.sub.2 is optionally susbtituted phenyl, or naphtyl; when Z is --SO.sub.2 --, R.sub.2 is C.sub.1-4 alkyl, phenyl-C.sub.1-4 -alkyl or optionally susbtituted phenyl.

  本发明涉及具有抗真菌活性的新口服活性唑类衍生物，其化学式为I 其中：X为CH或N；Ar代表用卤素和/或三氟甲基取代的苯基；Z为--C(=O)--或--SO.sub.2--；R.sub.1为CN、CO.sub.2 H、CO.sub.2 R.sub.7、CONR.sub.8 R.sub.9或CH.sub.2Y，然后R.sub.3为氢，或R.sub.1与R.sub.3一起形成化学式I'的环 其中B为O、羟基或氢；R.sub.4为C.sub.1-4烷基；R.sub.5、R.sub.6、R.sub.8和R.sub.9为氢或C.sub.1-4烷基；Y为--OH、--OR.sub.7、--OC(=O)R.sub.7、--NR.sub.8 R.sub.9、--NHC(=O)OR.sub.7；R.sub.7为C.sub.1-C.sub.4-烷基、苯基-C.sub.1-C.sub.4-烷基或可选择取代的苯基；当Z为--C(=O)--时，R.sub.2为可选择取代的苯基或萘基；当Z为--SO.sub.2--时，R.sub.2为C.sub.1-4烷基、苯基-C.sub.1-4-烷基或可选择取代的苯基。
• [EN] NEW PYRIMIDONE DERIVATIVES WITH ANTIFUNGAL ACTIVITY<br/>[FR] NOUVEAUX DERIVES PYRIMIDONE A ACTIVITE ANTIFONGIQUE
  申请人：J. URIACH & CIA. S.A.

  公开号：WO1997005130A1

  公开（公告）日：1997-02-13

  (EN) Compounds of general formula (I) and their salts and solvates are antifungal agents and as such are useful in the treatment of various fungal infections. Pharmaceutical compositions including these compounds and processes for their preparation are also provided.(FR) Les composés de la formule générale (I) et leurs sels et solvates sont des agents antifongiques. Il sont utiles pour le traitement de différentes infections fongiques. L'invention concerne également des compositions pharmaceutiques comprenant ces composés et des procédés permettant leur préparation.

  化合物的一般式（I）及其盐和溶剂物是抗真菌剂，因此可用于治疗各种真菌感染。还提供了包括这些化合物的制药组合物和其制备方法。
• Sulfonamides as antifungal agents
  申请人：J. Uriach & Cia. S.A.

  公开号：US05360813A1

  公开（公告）日：1994-11-01

  The present invention relates to new sulfonamides having the formula I: ##STR1## wherein: R.sup.1 represents an alkyl, aryl or heteroaryl group; R.sup.2 is hydrogen or an alkyl, aryl or heteroaryl group; or R.sup.1 and R.sup.2 may form a ring; R.sup.3 is hydrogen or may form an oxazolidine ring together with R.sup.2, and this ring may be optionally substituted by one or two alkyl, aryl or heteroaryl groups at the postion 2; R.sup.7 is hydrogen or alkyl; X is CH or N; Ar is a phenyl ring or a substituted phenyl ring. The invention also relates to a procedure for their preparation and to pharmaceutical and agrochemical compositions containing them. These compounds are antifungal agents.

  本发明涉及具有式I的新磺胺类化合物：##STR1## 其中：R1代表烷基，芳基或杂环芳基基团；R2为氢或烷基，芳基或杂环芳基基团；或R1和R2可以形成环；R3为氢或可以与R2一起形成噁唑啉环，该环在2位可以选择地被一个或两个烷基，芳基或杂环芳基基团取代；R7为氢或烷基；X为CH或N；Ar为苯环或取代苯环。本发明还涉及它们的制备方法以及含有它们的制药和农药组合物。这些化合物是抗真菌剂。