公开(公告)号：US06509339B2

公开(公告)日：2003-01-21

申请号：US09933094

申请日：2001-08-20

申请人： Jean-Paul René Marie Bosmans ,  Christopher John Love ,  Marc Gustaaf Celine Verdonck ,  Joannes Adrianus Jacobus Schuurkes

发明人： Jean-Paul René Marie Bosmans ,  Christopher John Love ,  Marc Gustaaf Celine Verdonck ,  Joannes Adrianus Jacobus Schuurkes

IPC分类号： C07D40514

CPC分类号： C07D401/06 ,  C07D211/22 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D417/14

摘要： 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 C2-6alkynyloxy; 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, C3-6cycloalkyl, 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.

摘要翻译： 本发明涉及配制N-氧化物形式的化合物，其药学上可接受的酸加成盐及其立体化学异构形式，其中R 1为C 1-6烷氧基，C 2-6烯氧基或C 2-6炔基氧基; R 2是氢或C 1-6烷氧基，或者当R 1和R 2一起形成式2的二价基团时，其中在所述二价基团中，一个或两个氢原子可以被C 1-6烷基取代，R 3是氢或卤素; L是C3-6环烷基，C5-6环烷酮，任选被芳基取代的C2-6烯基，或L是式-Alk-R4，-Alk-NR5R6，1-R6-4-哌啶基，Alk-X-R7， - Alk-YC（= O）-R9或-Alk-YC（= O）-NR11R12，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; R 7是氢，C 1-6烷基，羟基C 1-6烷基，C 3-6环烷基，Ar或Het 2; X是O，S，SO 2或NR 8; 所述R8为氢，C1-6烷基或Ar; R 9为氢，C 1-6烷基，C 3-6环烷基，Ar，ArC 1-6烷基，二（Ar）甲基，C 1-6烷氧基或羟基; Y是NR10或直接键; 所述R 10为氢，C 1-6烷基或Ar; R 11和R 12各自独立地为氢，C 1-6烷基，C 3-6环烷基，Ar或ArC 1-6烷基，或R 11和R 12与带有R 11和R 12的氮原子结合可以形成吡咯烷基或哌啶基环，其两者均被C 1-6烷基 ，氨基或单或

公开(公告)号：US06800628B2

公开(公告)日：2004-10-05

申请号：US10299317

申请日：2002-11-19

申请人： Jean-Paul René Marie Bosmans ,  Christopher John Love ,  Marc Gustaaf Celine Verdonck ,  Joannes Adrianus Jacobus Schuurkes

发明人： Jean-Paul René Marie Bosmans ,  Christopher John Love ,  Marc Gustaaf Celine Verdonck ,  Joannes Adrianus Jacobus Schuurkes

IPC分类号： A61K31501

CPC分类号： C07D401/06 ,  C07D211/22 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D417/14

摘要： 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.

摘要翻译： 本发明涉及配制N-氧化物形式的化合物，其药学上可接受的酸加成盐及其立体化学异构形式，其中R 1为C 1-6烷氧基，C 2-6烯氧基或C 2-6-26炔氧基; R 2是氢或C 1-6烷氧基，或者当R 1和R 2一起可以形成下式的二价基团时，其中在所述二价基团中，一个或两个氢原子可以被C 1-6烷基取代，R 3是氢或卤素; L是C3-6环烷基，C5-6环烷酮，任选被芳基取代的C 2-6链烯基，或L是式-Alk-R 4，-Alk-NR 5 R 6，1-R 6 其中每个Alk为C1（= O）-R9，-Alk-YC（= O）-NR11R12，其中每个Alk为C1 -12烷二基; R 4是氢，C 1-6烷基磺酰基氨基，C 3-6环烷基，C 5-6环烷酮，Ar-，二（Ar）甲基，Ar-氧基或Het 1。 R 5是氢或C 1-6烷基; R 6是Het 2; R 7是氢，C 1-6烷基，羟基C 1-6烷基，C 3-6环烷基，Ar或Het 2; X是O，S，SO 2或NR 8; 所述R 8为氢，C 1-6烷基或Ar; R 9是氢，C 1-6烷基，C 3-6环烷基，Ar，ArC 1-6烷基，二（Ar）甲基，C 1-6烷氧基或羟基; Y是NR 10或直接键; 所述R 10为氢，C 1-6烷基或Ar; R 11和R 12各自独立地为氢，C 1-6烷基，C 3-6环烷基，Ar或ArC 1-6烷基，或R 11和R 12与带有R 11和R 10的氮原子结合 可以形成任选被C

公开(公告)号：US06291481B1

公开(公告)日：2001-09-18

申请号：US09125901

申请日：1998-08-27

申请人： Jean-Paul René Marie Bosmans ,  Christopher John Love ,  Marc Gustaaf Celine Verdonck ,  Joannes Adrianus Jacobus Schuurkes

发明人： Jean-Paul René Marie Bosmans ,  Christopher John Love ,  Marc Gustaaf Celine Verdonck ,  Joannes Adrianus Jacobus Schuurkes

IPC分类号： A61K314523

CPC分类号： C07D401/06 ,  C07D211/22 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D417/14

摘要： Compounds of formula I the N-oxide forms, the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein the substituents are as described in the specification, and process 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.

摘要翻译： 式I化合物为N-氧化物形式，其药学上可接受的酸加成盐及其立体化学异构形式，其中取代基如说明书所述，制备所述产物的方法，包含所述产物的制剂及其作为药物的用途是 特别是用于治疗与胃排空障碍相关的病症。