(+/-)-2-chloro-α-(4-chlorophenyl)-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)-N'-hydroxybenzeneethanimidamide

• 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: (+/-)-2-chloro-α-(4-chlorophenyl)-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)-N'-hydroxybenzeneethanimidamide
• 英文别名: 2-[2-chloro-4-(3,5-dioxo-1,2,4-triazin-2-yl)phenyl]-2-(4-chlorophenyl)-N'-hydroxyethanimidamide
• 化学式: C₁₇H₁₃Cl₂N₅O₃
• 分子量: 406.228
• InChiKey: PWUJLPDGPVGDHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  克拉珠利 在 NaOCH₃ 、 羟胺 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 生成 (+/-)-2-chloro-α-(4-chlorophenyl)-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)-N'-hydroxybenzeneethanimidamide
  参考文献：
  名称：

  Novel IL-5 inhibiting 6-azauracil derivatives

  摘要：

  本发明涉及公式1的化合物，包括N-氧化物、药学上可接受的加合盐以及其立体化异构体形式，其中p和q为0、1、2、3或4，q也可以为5；X为O、S、NR3或直接键；R1为氢、羟基、卤素、可选择取代的氨基、可选择取代的C1-6烷基、C1-6烷氧基、C3-7环烷基或芳基；R2为芳基、Het1、C3-7环烷基、可选择取代的C1-6烷基；如果X为O、S或NR3，则R2也可以是羰基或硫代羰基连接的取代基；R3为氢或C1-4烷基；R4和R5独立地为可选择取代的C1-6烷基、卤素、羟基、巯基、C1-6烷氧基、C1-6烷硫基、C1-6烷基羰氧基、芳基、氰基、硝基、Het3、R6或NR7R8；R6为取代磺酰基或亚砜基；R7和R8为氢、可选择取代的C1-4烷基、芳基、羰基或硫代羰基连接的取代基、C3-7环烷基、Het3和R6；R9和R10各自独立地选自氢、可选择取代的C1-4烷基、苯基、羰基或硫代羰基连接的取代基、C3-7环烷基、Het3和R6；R11为羟基、巯基、氰基、硝基、卤素、三卤甲基、C1-4烷氧基、羧基、C1-4烷氧羰基、三卤代C1-4烷基磺酰氧基、R6、NR7R8、C(═O)NR7R8、芳基、芳氧基、芳基羰基、C3-7环烷基、C3-7环烷氧基、邻苯二甲酰亚胺-2-基、Het3和C(═O)Het3；R12和R13各自独立地选自氢、可选择取代的C1-4烷基、苯基、羰基或硫代羰基连接的取代基、C3-7环烷基和R6；芳基为可选择取代的苯基；Het1、Het2和Het3为可选择取代的杂环；以及其制备方法和包含它们的组合物。进一步涉及它们作为药物的用途。

  公开号：

  US20020072603A1

文献信息

• Novel IL-5 inhibiting 6-azauracil derivatives for marking and identifying receptors and imaging organs
  申请人：Lacrampe Fernand Armand Jean

  公开号：US20050090495A1

  公开（公告）日：2005-04-28

  The present invention is concerned with the compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, p and q are 0, 1, 2, 3 or 4 and q is also 5; X is O, S, NR 3 or a direct bond; R 1 is hydrogen, hydroxy, halo, optionally substituted amino, optionally substituted C 1-6 alkyl, C 1-6 alkyloxy, C 3-7 cycloalkyl or aryl; R 2 is aryl, Het 1 , C 3-7 cycloalkyl, optionally substituted C 1-6 alkyl; and if X is O, S or NR 3 , then R 2 may also be a carbonyl or thiocarbonyl linked substituent; R 3 is hydrogen or C 1-4 allyl; R 4 and R 5 independently are optionally substituted C 1-6 alkyl, halo, hydroxy, mercapto, C 1-6 alkyloxy, C 1-6 alkylthio, C 1-6 alkylcarbonyloxy, aryl, cyano, nitro, Het 3 , R 6 or NR 7 R 8 ; R 6 is substituted sulfonyl or sulfinyl; R 7 and R 8 are hydrogen, optionally substituted C 1-4 alkyl, aryl, a carbonyl or thiocarbonyl linked substituent, C 3-7 cycloalkyl, Het 3 and R 6 ; R 9 and R 10 are each independently selected from hydrogen, optionally substituted C 1-4 alkyl, phenyl, a carbonyl or thiocarbonyl linked substituent, C 3-7 cycloalkyl, Het 3 and R 6 ; R 11 is hydroxy, mercapto, cyano, nitro, halo, trihalomethyl, C 1-4 alkyloxy, carboxyl, C 1-4 alkyloxycarbonyl, trihaloC 1-4 alkylsulfonyloxy, R 6 , NR 7 R 8 , C(═O)NR 7 R 3 , aryl, aryloxy, arylcarbonyl, C 3-7 cycloalkyl, C 3-7 cycloalkyloxy, phthalimide-2-yl, Het 3 and C(═O)Het 3 ; R 12 and R 13 are each independently selected from hydrogen, optionally substituted C 1-4 alkyl, phenyl, a carbonyl or thiocarbonyl linked substituent, C 3-7 cycloalkyl and R 6 ; aryl is optionally substituted phenyl; Het 1 , Het 2 and Het 3 are optionally substituted heterocycles; to processes for their preparation and compositions comprising them. It further relates to their use as a medicine.

  本发明涉及式子的化合物，其中N-氧化物，药学上可接受的加成盐和其立体化学异构体，p和q为0、1、2、3或4，而q也可以为5；X为O、S、NR3或直接键；R1为氢、羟基、卤素、可选取代氨基、可选取代的C1-6烷基、C1-6烷氧基、C3-7环烷基或芳基；R2为芳基、Het1、C3-7环烷基、可选取代的C1-6烷基；如果X为O、S或NR3，则R2还可以是一个与羰基或硫代羰基连接的取代基；R3为氢或C1-4烯丙基；R4和R5独立地为可选取代的C1-6烷基、卤素、羟基、巯基、C1-6烷氧基、C1-6烷硫基、C1-6烷基羰氧基、芳基、氰基、硝基、Het3、R6或NR7R8；R6为取代磺酰基或亚磺酰基；R7和R8为氢、可选取代的C1-4烷基、芳基、与羰基或硫代羰基连接的取代基、C3-7环烷基、Het3和R6；R9和R10各自独立地选自氢、可选取代的C1-4烷基、苯基、与羰基或硫代羰基连接的取代基、C3-7环烷基、Het3和R6；R11为羟基、巯基、氰基、硝基、卤素、三卤甲基、C1-4烷氧基、羧基、C1-4烷氧基羰基、三卤代C1-4烷基磺酰氧基、R6、NR7R8、C（═O）NR7R3、芳基、芳氧基、芳基羰基、C3-7环烷基、C3-7环烷氧基、邻二苯酰胺基-2-基、Het3和C（═O）Het3；R12和R13各自独立地选自氢、可选取代的C1-4烷基、苯基、与羰基或硫代羰基连接的取代基、C3-7环烷基和R6；芳基为可选取代的苯基；Het1、Het2和Het3为可选取代的杂环；以及制备它们的方法和包含它们的组合物。此外，本发明还涉及它们作为药品的用途。
• IL-5 inhibiting 6-azauracil derivatives
  申请人：Lacrampe Jean Fernand Armand

  公开号：US06867207B2

  公开（公告）日：2005-03-15

  The present invention is concerned with the compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, p and q are 0, 1, 2, 3 or 4 and q is also 5; X is O, S, NR 3 or a direct bond; R 1 is hydrogen, hydroxy, halo, optionally substituted amino, optionally substituted C 1-6 alkyl, C 1-6 alkyloxy, C 3-7 cycloalkyl or aryl; R 2 is aryl, Het 1 , C 3-7 cycloalkyl, optionally substituted C 1-6 alkyl; and if X is O, S or NR 3 , then R 2 may also be a carbonyl or thiocarbonyl linked substituent; R 3 is hydrogen or C 1-4 alkyl; R 4 and R 5 independently are optionally substituted C 1-6 alkyl, halo, hydroxy, mercapto, C 1-6 alkyloxy, C 1-6 akylthio, C 1-6 alkylcarbonyloxy, aryl, cyano, nitro, Het 3 , R 6 or NR 7 R 8 ; R 6 is substituted sulfonyl or sulfinyl; R 7 and R 8 are hydrogen, optionally substituted C 1-4 alkyl, aryl, a carbonyl or thiocarbonyl linked substituent, C 3-7 cycloalkyl, Het 3 and R 6 ; R 9 and R 10 are each independently selected from hydrogen, optionally substituted C 1-4 alkyl, phenyl, a carbonyl or thiocarbonyl linked substituent, C 3-7 cycloalkyl, Het 3 and R 6 ; R 11 is hydroxy, mercapto, cyano, nitro, halo, trihalomethyl, C 1-4 alkyloxy, carboxyl, C 1-4 alkyloxycarbonyl, trihaloC 1-4 alkylsulfonyloxy, R 6 , NR 7 R 8 , C(═O)NR 7 R 8 , aryl, aryloxy, arylcarbonyl, C 3-7 cycloalkyl, C 3-7 cycloalkyloxy, phthalimide-2-yl, Het 3 and C(═O)Het 3 ; R 12 and R 13 are each independently selected from hydrogen, optionally substituted C 1-4 alkyl, phenyl, a carbonyl or thiocarbonyl linked substituent, C 3-7 cycloalkyl and R 6 ; aryl is optionally substituted phenyl; Het 1 , Het 2 and Het 3 are optionally substituted heterocycles; to processes for their preparation and compositions comprising them. It further relates to their use as a medicine.

  本发明涉及式为的化合物，其N-氧化物，药学上可接受的加成盐和其立体化学异构体，其中p和q为0、1、2、3或4，q也可以为5；X为O、S、NR3或直接键；R1为氢、羟基、卤素、可选取代的氨基、可选取代的C1-6烷基、C1-6烷氧基、C3-7环烷基或芳基；R2为芳基、Het1、C3-7环烷基、可选取代的C1-6烷基；如果X为O、S或NR3，则R2也可以是羰基或硫代羰基连接的取代基；R3为氢或C1-4烷基；R4和R5独立地为可选取代的C1-6烷基、卤素、羟基、巯基、C1-6烷氧基、C1-6烷基硫基、C1-6烷基羰酸酯、芳基、氰基、硝基、Het3、R6或NR7R8；R6为取代的磺酰基或亚磺酰基；R7和R8为氢、可选取代的C1-4烷基、芳基、羰基或硫代羰基连接的取代基、C3-7环烷基、Het3和R6；R9和R10各自独立地选自氢、可选取代的C1-4烷基、苯基、羰基或硫代羰基连接的取代基、C3-7环烷基、Het3和R6；R11为羟基、巯基、氰基、硝基、卤素、三卤甲基、C1-4烷氧基、羧基、C1-4烷氧羰基、三卤代C1-4烷基磺酰氧基、R6、NR7R8、C(═O)NR7R8、芳基、芳氧基、芳基羰基、C3-7环烷基、C3-7环烷氧基、邻苯二酰亚胺-2-基和C(═O)Het3；R12和R13各自独立地选自氢、可选取代的C1-4烷基、苯基、羰基或硫代羰基连接的取代基、C3-7环烷基和R6；芳基为可选取代的苯基；Het1、Het2和Het3为可选取代的杂环；以及它们的制备方法和包含它们的组合物。它进一步涉及它们作为药物的使用。
• IL-5 INHIBITING 6-AZAURACIL DERIVATIVES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1000040B1

  公开（公告）日：2007-06-13
• US6867207B2
  申请人：——

  公开号：US6867207B2

  公开（公告）日：2005-03-15
• Novel IL-5 inhibiting 6-azauracil derivatives
  申请人：——

  公开号：US20020072603A1

  公开（公告）日：2002-06-13

  The present invention is concerned with the compounds of formula 1 the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, p and q are 0, 1, 2, 3 or 4 and q is also 5; X is O, S, NR 3 or a direct bond; R 1 is hydrogen, hydroxy, halo, optionally substituted amino, optionally substituted C 1-6 alkyl, C 1-6 alkyloxy, C 3-7 cycloalkyl or aryl; R 2 is aryl, Het 1 , C 3-7 cycloalkyl, optionally substituted C 1-6 alkyl; and if X is O, S or NR 3 , then R 2 may also be a carbonyl or thiocarbonyl linked substituent; R 3 is hydrogen or C 1-4 alkyl; R 4 and R 5 independently are optionally substituted C 1-6 alkyl, halo, hydroxy, mercapto, C 1-6 alkyloxy, C 1-6 akylthio, C 1-6 alkylcarbonyloxy, aryl, cyano, nitro, Het 3 , R 6 or NR 7 R 8 ; R 6 is substituted sulfonyl or sulfinyl; R 7 and R 8 are hydrogen, optionally substituted C 1-4 alkyl, aryl, a carbonyl or thiocarbonyl linked substituent, C 3-7 cycloalkyl, Het 3 and R 6 ; R 9 and R 10 are each independently selected from hydrogen, optionally substituted C 1-4 alkyl, phenyl, a carbonyl or thiocarbonyl linked substituent, C 3-7 cycloalkyl, Het 3 and R 6 ; R 11 is hydroxy, mercapto, cyano, nitro, halo, trihalomethyl, C 1-4 alkyloxy, carboxyl, C 1-4 alkyloxycarbonyl, trihaloC 1-4 alkylsulfonyloxy, R 6 , NR 7 R 8 , C(═O)NR 7 R 8 , aryl, aryloxy, arylcarbonyl, C 3-7 cycloalkyl, C 3-7 cycloalkyloxy, phthalimide-2-yl, Het 3 and C(═O)Het 3 ; R 12 and R 13 are each independently selected from hydrogen, optionally substituted C 1-4 alkyl, phenyl, a carbonyl or thiocarbonyl linked substituent, C 3-7 cycloalkyl and R 6 ; aryl is optionally substituted phenyl; Het 1 , Het 2 and Het 3 are optionally substituted heterocycles; to processes for their preparation and compositions comprising them. It further relates to their use as a medicine.

  本发明涉及公式1的化合物，包括N-氧化物、药学上可接受的加合盐以及其立体化异构体形式，其中p和q为0、1、2、3或4，q也可以为5；X为O、S、NR3或直接键；R1为氢、羟基、卤素、可选择取代的氨基、可选择取代的C1-6烷基、C1-6烷氧基、C3-7环烷基或芳基；R2为芳基、Het1、C3-7环烷基、可选择取代的C1-6烷基；如果X为O、S或NR3，则R2也可以是羰基或硫代羰基连接的取代基；R3为氢或C1-4烷基；R4和R5独立地为可选择取代的C1-6烷基、卤素、羟基、巯基、C1-6烷氧基、C1-6烷硫基、C1-6烷基羰氧基、芳基、氰基、硝基、Het3、R6或NR7R8；R6为取代磺酰基或亚砜基；R7和R8为氢、可选择取代的C1-4烷基、芳基、羰基或硫代羰基连接的取代基、C3-7环烷基、Het3和R6；R9和R10各自独立地选自氢、可选择取代的C1-4烷基、苯基、羰基或硫代羰基连接的取代基、C3-7环烷基、Het3和R6；R11为羟基、巯基、氰基、硝基、卤素、三卤甲基、C1-4烷氧基、羧基、C1-4烷氧羰基、三卤代C1-4烷基磺酰氧基、R6、NR7R8、C(═O)NR7R8、芳基、芳氧基、芳基羰基、C3-7环烷基、C3-7环烷氧基、邻苯二甲酰亚胺-2-基、Het3和C(═O)Het3；R12和R13各自独立地选自氢、可选择取代的C1-4烷基、苯基、羰基或硫代羰基连接的取代基、C3-7环烷基和R6；芳基为可选择取代的苯基；Het1、Het2和Het3为可选择取代的杂环；以及其制备方法和包含它们的组合物。进一步涉及它们作为药物的用途。