[1-[3-(3-chloro-6-oxo-1 (6H)-pyridazinyl)propyl]-4-piperidinyl]methyl 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylate | 196308-18-6

• 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: [1-[3-(3-chloro-6-oxo-1 (6H)-pyridazinyl)propyl]-4-piperidinyl]methyl 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylate
• 英文别名: [1-[3-(3-chloro-6-oxo-1(6H)-pyridazinyl)propyl]-4-piperidinyl]methyl 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylate；[1-[3-(3-chloro-6-oxopyridazin-1-yl)propyl]piperidin-4-yl]methyl 4-amino-5-chloro-2,3-dihydro-1-benzofuran-7-carboxylate
• CAS: 196308-18-6
• 化学式: C₂₂H₂₆Cl₂N₄O₄
• 分子量: 481.379
• InChiKey: YCKSXEPJXNDHEB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  97.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  咪唑 、 1-[(4-Amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]-1H-imidazole 、 6-chloro-2-[3-[4-(hydroxymethyl)-1-piperidinyl]propyl]-3(2H)-pyridazinone 在 NaH 作用下， 以 四氢呋喃 为溶剂， 以1.88 g (39%)的产率得到[1-[3-(3-methyl-6-oxo-1(6H)-pyridazinyl)propyl]-4-piperidinyl]-methyl 7-amino-6-chloro-1,3-benzodioxole-4-carboxylate
  参考文献：
  名称：

  N-substituted 4-(4′-aminobenzoyl)-oxymethyl)-piperidines having gastric prokinetic properties

  摘要：

  本发明涉及化合物I的N-氧化物形式、药用可接受的酸盐加成物和其立体化学异构体形式，其中取代基如说明书所述，以及制备该产品的过程、包含该产品的制剂以及其用作药物的用途，特别是用于治疗与胃排空障碍有关的疾病。

  公开号：

  US06291481B1
• 作为试剂：
  描述：

  咪唑 、 6-chloro-2-[3-[4-(hydroxymethyl)-1-piperidinyl]propyl]-3(2H)-pyridazinone 、 sodium;hydride 、 1-[(4-Amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]-1H-imidazole 在 氮气 、 水 、 二氯甲烷 、 silica gel 、 dichloromethane hexane 、 ammonia methanol 、 乙腈 、 [1-[3-(3-chloro-6-oxo-1 (6H)-pyridazinyl)propyl]-4-piperidinyl]methyl 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylate 、 [1-[3-(3-methyl-6-oxo-1(6H)-pyridazinyl)propyl]-4-piperidinyl]-methyl 7-amino-6-chloro-1,3-benzodioxole-4-carboxylate 作用下， 以 四氢呋喃 为溶剂， 反应 0.42h， 以yielding 1.88 g (39%) of [1-[3-(3-chloro-6-oxo-1(6H)-pyridazinyl)propyl]-4-piperidinyl]methyl 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylate (compound 21, mp: 137° C.) In a similar way, [1-[3-(3-methyl-6-oxo-1(6H)-pyridazinyl)propyl]-4-piperidinyl]-methyl 7-amino-6-chloro-1,3-benzodioxole-4-carboxylate (compound 22)的产率得到[1-[3-(3-chloro-6-oxo-1 (6H)-pyridazinyl)propyl]-4-piperidinyl]methyl 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylate
  参考文献：
  名称：

  N-substituted 4-((4′-aminobenzoyl)-oxymethyl)-piperidines having gastric prokinetic properties

  摘要：

  本发明涉及公式N-氧化物形式的化合物，药学上可接受的酸盐加成物和其立体化学异构体形式，其中R1是C1-6烷氧基，C2-6烯氧基或C2-6炔氧基；R2是氢或C1-6烷氧基，或当R1和R2一起取时，它们可以形成公式的二价基团，其中在该二价基团中，一个或两个氢原子可以被C1-6烷基取代，R3是氢或卤素；L是C3-6环烷基，C5-6环烷酮，C2-6烯基（可选地被芳基取代），或L是公式-Alk-R4，-Alk-NR5R6，1-R6-4-哌啶基，Alk-X—R7，-Alk-Y—C（═O）—R9，或-Alk-Y—C（═O）—NR11R12的基团，其中每个Alk是C1-12烷二基；R4是氢，C1-6烷基磺酰氨基，C3-6环烷基，C5-6环烷酮，Ar-，二（Ar）甲基，Ar-氧基或Het1；R5是氢或C1-6烷基；R6是Het2；R7是氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基，Ar或Het2；X是O，S，SO2或NR8；其中R8是氢，C1-6烷基或Ar；R9是氢，C1-6烷基，C3-6环烷基，Ar，ArC1-6烷基，二（Ar）甲基，C1-6烷氧基或羟基；Y是NR10或直接键；其中R10是氢，C1-6烷基或Ar；R11和R12各自独立地是氢，C1-6烷基，C3-6环烷基，Ar或ArC1-6烷基，或R11和R12与携带R11和R12的氮原子结合，可以形成带有C1-6烷基，氨基或单或双（C1-6烷基）氨基的吡咯烷基或哌啶烷基环，或R11和R12与携带R11和R12的氮结合，可以形成带有C1-6烷基的哌嗪基或4-吗啉基基团，两者都可以选择地被C1-6烷基取代。公开了制备该产品的过程，包含该产品的制剂以及其作为药物的用途，特别是用于治疗与胃排空障碍有关的疾病。

  公开号：

  US06509339B2

文献信息

• Novel esters of 1, 4-disubstituted piperidine derivatives
  申请人：——

  公开号：US20020042430A1

  公开（公告）日：2002-04-11

  This invention concerns the compounds of formula 1 the N-oxide forms, the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein R 1 is C 1-6 alkyloxy, C 2-6 alkenyloxy or C 2-6 alkynyloxy; R 2 is hydrogen or C 1-6 alkyloxy, or when taken together R 1 and R 2 may form a bivalent radical of formula wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C 1-6 alkyl, R 3 is hydrogen or halo; L is C 3-6 cycloalkyl, C 5-6 cycloalkanone, C 2-6 alkenyl optionally substituted with aryl, or L is a radical of formula —Alk—R 4 , —Alk—NR 5 R 6 , 1-R 6 -4-piperidinyl, Alk—X—R 7 , —Alk—Y—C(═O)—R 9 , or —Alk—Y—C(═O)—NR 11 R 12 wherein each Alk is C 1-12 alkanediyl; R 4 is hydrogen, C 1-6 alkylsulfonylamino, C 3-6 cycloalkyl, C 5-6 cycloalkanone, Ar—, di(Ar)methyl, Ar—oxy- or Het 1 ; R 5 is hydrogen or C 1-6 alkyl; R 6 is Het 2 ; R 7 is hydrogen, C 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 cycloalkyl, Ar or Het 2 ; X is O, S, SO 2 or NR 8 ; said R 8 being hydrogen, C 1-6 alkyl or Ar; R 9 is hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, Ar, ArC 1-6 alkyl, di(Ar)methyl, C 1-6 alkyloxy or hydroxy; Y is NR 10 or a direct bond; said R 10 being hydrogen, C 1-6 alkyl or Ar; R 11 and R 12 each independently are hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, Ar or ArC 1-6 alkyl, or R 11 and R 12 combined with the nitrogen atom bearing R 11 and R 12 may form a pyrrolidinyl or piperidinyl ring both being optionally substituted with C 1-6 alkyl, amino or mono or di(C 1-6 alkyl)amino, or said R 11 and R 12 combined with the nitrogen bearing R 11 and R 12 may form a piperazinyl or 4-morpholinyl radical both being optionally substituted with C 1-6 alkyl. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impairment of gastric emptying.

  本发明涉及公式1的化合物，其N-氧化物形式，药学上可接受的酸加成盐和立体化学异构体形式，其中R1是C1-6烷氧基，C2-6烯氧基或C2-6炔氧基；R2是氢或C1-6烷氧基，或当R1和R2一起取时，它们可以形成公式的双价基团，在所述双价基团中，一个或两个氢原子可以被C1-6烷基取代，R3是氢或卤素；L是C3-6环烷基，C5-6环烷酮，C2-6烯基，可选地取代芳基，或L是公式—Alk—R4，—Alk—NR5R6，1-R6-4-哌啶基，Alk—X—R7，—Alk—Y—C(═O)—R9或—Alk—Y—C(═O)—NR11R12的基团，其中每个Alk是C1-12烷二基；R4是氢，C1-6烷基磺酰胺基，C3-6环烷基，C5-6环烷酮，Ar—，二(Ar)甲基，Ar—氧基或Het1；R5是氢或C1-6烷基；R6是Het2；R7是氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基，Ar或Het2；X是O，S，SO2或NR8；所述的R8是氢，C1-6烷基或Ar；R9是氢，C1-6烷基，C3-6环烷基，Ar，ArC1-6烷基，二(Ar)甲基，C1-6烷氧基或羟基；Y是NR10或直接键；所述的R10是氢，C1-6烷基或Ar；R11和R12各自独立地是氢，C1-6烷基，C3-6环烷基，Ar或ArC1-6烷基，或R11和R12与携带R11和R12的氮原子结合，可以形成一个吡咯啉基或哌啶基，两者都可以选择地取代C1-6烷基，氨基或单或双(C1-6烷基)氨基，或所述的R11和R12与携带R11和R12的氮原子结合，可以形成一个哌嗪基或4-吗啉基基团，两者都可以选择地取代C1-6烷基。公开了制备所述产品的过程，包括所述产品的配方以及它们作为药物的用途，特别是用于治疗与胃排空障碍有关的疾病。
• Novel N-substituted 4-((-4'-aminobenzoyl)-oxymethyl)-piperidines having gastric prokinetic properties
  申请人：——

  公开号：US20030153573A1

  公开（公告）日：2003-08-14

  This invention concerns the compounds of formula 1 the N-oxide forms, the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein R 1 is C 1-6 alkyloxy, C 2-6 alkenyloxy or C 2-6 alkynyloxy; R 2 is hydrogen or C 1-6 alkyloxy, or when taken together R 1 and R 2 may form a bivalent radical of formula wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C 1-6 alkyl, R 3 is hydrogen or halo; L is C 3-6 cycloalkyl, C 5-6 cycloalkanone, C 2-6 alkenyl optionally substituted with aryl, or L is a radical of formula -Alk—R 4 , -Alk—NR 5 R 6 , 1-R 6 -4-piperidinyl, Alk-X—R 7 , -Alk—Y—C(═O)—R 9 , or -Alk—Y—C(═O)—NR 11 R 12 wherein each Alk is C 1-12 alkanediyl; R 4 is hydrogen, C 1-6 alkylsulfonylamino, C 3-6 cycloalkyl, C 5-6 cycloalkanone, Ar-, di(Ar)methyl, Ar-oxy- or Het 1 ; R 5 is hydrogen or C 1-6 alkyl; R 6 is Het 2 ; R 7 is hydrogen, C 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 cycloalkyl, Ar or Het 2 ; X is O, S, SO 2 or NR 8 ; said R 8 being hydrogen, C 1-6 alkyl or Ar; R 9 is hydrogen, C 1-6 alkyl, C 3-6 cyclo-alkyl, Ar, ArC 1-6 alkyl, di(Ar)methyl, C 1-6 alkyloxy or hydroxy; Y is NR 10 or a direct bond; said R 10 being hydrogen, C 1-6 alkyl or Ar; R 11 and R 12 each independently are hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, Ar or ArC 1-6 alkyl, or R 11 and R 12 combined with the nitrogen atom bearing R 11 and R 12 may form a pyrrolidinyl or piperidinyl ring both being optionally substituted with C 1-6 alkyl, amino or mono or di(C 1-6 alkyl)amino, or said R 11 and R 12 combined with the nitrogen bearing R 11 and R 12 may form a piperazinyl or 4-morpholinyl radical both being optionally substituted with C 1-6 alkyl. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impairment of gastric emptying.

  本发明涉及公式1的化合物，其N-氧化物形式，药学上可接受的酸加成盐和其立体化学异构体形式，其中R1是C1-6烷氧基，C2-6烯氧基或C2-6炔氧基; R2是氢或C1-6烷氧基，或当R1和R2一起取时，它们可以形成公式的二价基团，在所述的二价基团中，一个或两个氢原子可以被C1-6烷基取代，R3是氢或卤素; L是C3-6环烷基，C5-6环戊酮，C2-6烯基，可选地用芳基取代，或L是公式-Alk-R4，-Alk-NR5R6，1-R6-4-哌啶基，Alk-X-R7，-Alk-Y-C(═O)-R9，或-Alk-Y-C(═O)-NR11R12的基团，其中每个Alk是C1-12烷二基基；R4是氢，C1-6烷基磺酰胺基，C3-6环烷基，C5-6环戊酮，Ar-，二(Ar)甲基，Ar-氧基或Het1; R5是氢或C1-6烷基；R6是Het2; R7是氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基，Ar或Het2; X是O，S，SO2或NR8; R8是氢，C1-6烷基或Ar; R9是氢，C1-6烷基，C3-6环烷基，Ar，ArC1-6烷基，二(Ar)甲基，C1-6烷氧基或羟基; Y是NR10或直接键; R10是氢，C1-6烷基或Ar; R11和R12各自独立地是氢，C1-6烷基，C3-6环烷基，Ar或ArC1-6烷基，或R11和R12与带R11和R12的氮原子结合，可以形成取代为C1-6烷基，氨基或单或二(C1-6烷基)氨基的吡咯啉基或哌啶基环，或R11和R12与带R11和R12的氮结合，可以形成取代为C1-6烷基的哌嗪基或4-吗啉基基团。公开了制备这些产品的过程，包括这些产品的制剂及其作为药物的用途，特别是用于治疗与胃排空障碍有关的疾病。
• N-substituted 4-((-4′-aminobenzoyl)-oxymethyl)-piperidines having gastric prokinetic properties
  申请人：Janssen Pharmaceutica N.V.

  公开号：US06800628B2

  公开（公告）日：2004-10-05

  This invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein R1 is C1-6alkyloxy, C2-6alkenyloxy or C2-26alkynyloxy; R2 is hydrogen or C1-6alkyloxy, or when taken together R1 and R2 may form a bivalent radical of formula wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C1-6alkyl, R3 is hydrogen or halo; L is C3-6cycloalkyl, C5-6cycloalkanone, C2-6alkenyl optionally substituted with aryl, or L is a radical of formula —Alk—R4, —Alk—NR5R6, 1-R6-4-piperidinyl, Alk—X—R7, —Alk—Y—C(═O)—R9, or —Alk—Y—C(═O)—NR11R12 wherein each Alk is C1-12alkanediyl; R4 is hydrogen, C1-6alkylsulfonylamino, C3-6cycloalkyl, C5-6cycloalkanone, Ar—, di(Ar)methyl, Ar-oxy- or Het1; R5 is hydrogen or C1-6alkyl; R6 is Het2; R7 is hydrogen, C1-6alkyl, hydroxyC1-6alkyl, C3-6cycloalkyl, Ar or Het2; X is O, S, SO2 or NR8; said R8 being hydrogen, C1-6alkyl or Ar; R9 is hydrogen, C1-6alkyl, C3-6cyclo-alkyl, Ar, ArC1-6alkyl, di(Ar)methyl, C1-6alkyloxy or hydroxy; Y is NR10 or a direct bond; said R10 being hydrogen, C1-6alkyl or Ar; R11 and R12 each independently are hydrogen, C1-6alkyl, C3-6cycloalkyl, Ar or ArC1-6alkyl, or R11 and R12 combined with the nitrogen atom bearing R11 and R12 may form a pyrrolidinyl or piperidinyl ring both being optionally substituted with C1-6alkyl, amino or mono or di(C1-6alkyl)amino, or said R11 and R12 combined with the nitrogen bearing R11 and R12 may form a piperazinyl or 4-morpholinyl radical both being optionally substituted with C1-6alkyl. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impairment of gastric emptying.

  本发明涉及式N-氧化物形式的化合物、药学上可接受的酸加成盐和其立体化学异构体形式，其中R1是C1-6烷氧基、C2-6烯氧基或C2-26炔氧基；R2是氢或C1-6烷氧基，或当R1和R2一起取时，它们可以形成式的二价基团，其中在所述的二价基团中，一个或两个氢原子可以被C1-6烷基取代，R3是氢或卤素；L是C3-6环烷基、C5-6环戊酮、C2-6烯基（可以选择地被芳基取代），或L是式的基团，其中每个Alk是C1-12烷二基；R4是氢、C1-6烷基磺酰氨基、C3-6环烷基、C5-6环戊酮、Ar-、二（Ar）甲基、Ar氧基或Het1；R5是氢或C1-6烷基；R6是Het2；R7是氢、C1-6烷基、羟基C1-6烷基、C3-6环烷基、Ar或Het2；X是O、S、SO2或NR8；其中R8是氢、C1-6烷基或Ar；R9是氢、C1-6烷基、C3-6环烷基、Ar、ArC1-6烷基、二（Ar）甲基、C1-6烷氧基或羟基；Y是NR10或直接键；其中R10是氢、C1-6烷基或Ar；R11和R12各自独立地是氢、C1-6烷基、C3-6环烷基、Ar或ArC1-6烷基，或R11和R12与携带R11和R12的氮原子结合，可以形成带有C1-6烷基、氨基或单个或双个（C1-6烷基）氨基的吡咯啉基环或哌啶基环，或者R11和R12与携带R11和R12的氮原子结合，可以形成带有C1-6烷基的哌嗪基或4-吗啉基基团，两者都可以选择地被C1-6烷基取代。公开了制备这些产品的方法、包含这些产品的配方以及它们作为药物的使用，特别是用于治疗与胃排空障碍有关的疾病。
• N-SUBSTITUTED 4-((4'-AMINOBENZOYL)-OXYMETHYL)-PIPERIDINES HAVING GASTRIC PROKINETIC PROPERTIES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0885190B1

  公开（公告）日：2003-05-07
• US6291481B1
  申请人：——

  公开号：US6291481B1

  公开（公告）日：2001-09-18