公开(公告)号：US07622581B2

公开(公告)日：2009-11-24

申请号：US11568840

申请日：2005-05-17

申请人： Bart Rudolf Romanie Kesteleyn ,  Sandrine Marie Helene Vendeville ,  Natalie Maria Francisca Kindermans ,  Dominique Louis Nestor Ghislain Surleraux ,  Pierre Jean-Marie Bernard Raboisson ,  Piet Tom Bert Paul Wigerinck ,  Annick Ann Peeters

发明人： Bart Rudolf Romanie Kesteleyn ,  Sandrine Marie Helene Vendeville ,  Natalie Maria Francisca Kindermans ,  Dominique Louis Nestor Ghislain Surleraux ,  Pierre Jean-Marie Bernard Raboisson ,  Piet Tom Bert Paul Wigerinck ,  Annick Ann Peeters

IPC分类号： C07D471/00

CPC分类号： C07D471/04

摘要： This invention concerns the compounds the N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein X is NR2, O, S, SO, SO2; R1 is hydrogen, cyano, halo, substituted carbonyl, methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; n is 1, 2 or 3; R2 is hydrogen, aryl substituted with a radical —COOR4; or R2 is substituted C1-10alkyl, C2-20alkenyl or C3-7cycloalkyl; or R2 is a radical of formula: —CpH2p—CH(OR14)—CqH2q—R15 (b-3); —CH2—CH2—(O—CH2—CH2)m—OR14 (b-4); —CH2—CH2—(O—CH2—CH2)m—NR5aR5b (b-5); -a1=a2-a3=a4- is —CH═CH—CH═CH—; —N═CH—CH═CH—; —CH═N—CH═CH—; —CH═CH—N═CH—; —CH═CH—CH═N— (c-5); wherein one of the hydrogen atoms in (c-1)-(c-5) is replaced by particular radicals; R3 is nitro, cyano, amino, halo, hydroxy, C1-4alkyloxy, hydroxycarbonyl, substituted carbonyl, methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, N-hydroxy-methanimidamidyl or Het1.

摘要翻译： 本发明涉及N-氧化物，盐，立体异构形式，外消旋混合物，前药，酯和代谢物的化合物，其中X是NR 2，O，S，SO，SO 2; R 1是氢，氰基，卤素，取代的羰基，甲酰亚胺基，N-羟基 - 甲酰亚胺基，单或二（C 1-4烷基）甲酰亚胺基，Het1或Het2; n为1,2或3; R2是氢，被基团-COOR4取代的芳基; 或R 2为取代的C 1-10烷基，C 2-20烯基或C 3-7环烷基; 或R 2是下式的基团：-CpH 2 -p-CH（OR 14）-C≡H2 q-R 15（b-3）; -CH 2 -CH 2 - （O-CH 2 -CH 2）m -OR 14（b-4）; -CH 2 -CH 2 - （O-CH 2 -CH 2）m -NR 5 a R 5b（b-5）; -a1 = a2-a3 = a4-是-CH-CH-CH-CH-; -N-CH-CH-CH-; -CH-N-CH-CH-; -CH-CH-N-CH-; -CH-CH-CH-N-（c-5）; （c-1） - （c-5）中的一个氢原子被特定基团取代; R3是硝基，氰基，氨基，卤素，羟基，C1-4烷氧基，羟基羰基，取代的羰基，甲酰亚胺基，单或二（C1-4烷基）甲嘧磺酰氨基，N-羟基 - 甲亚胺酰氨基或Het1。

公开(公告)号：US07622582B2

公开(公告)日：2009-11-24

申请号：US11569108

申请日：2005-05-17

申请人： Bart Rudolf Romanie Kesteleyn ,  Wim Van De Vreken ,  Dominique Louis Nestor Ghislain Surleraux ,  Sandrine Marie Helene Vendeville ,  Pierre Jean-Marie Bernard Raboisson ,  Piet Tom Bert Paul Wigerinck ,  Annick Ann Peeters

发明人： Bart Rudolf Romanie Kesteleyn ,  Wim Van De Vreken ,  Dominique Louis Nestor Ghislain Surleraux ,  Sandrine Marie Helene Vendeville ,  Pierre Jean-Marie Bernard Raboisson ,  Piet Tom Bert Paul Wigerinck ,  Annick Ann Peeters

IPC分类号： C07D491/00

CPC分类号： C07D471/04 ,  C07D491/04 ,  C07D491/14

摘要： 4-substituted 1,5-dihydro-pyrido[3,2-b]indol-2-ones of formula (I): the N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein n is 1, 2 or 3; R1 is hydrogen, cyano, halo, substituted carbonyl, methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; X is NR2, O, S, SO, SO2; R2 is hydrogen, C1-10alkyl, C2-10alkenyl, C3-7cycloalkyl, which are optionally substituted; R2 is aryl substituted with —COOR4; or R2 is: —CpH2p—CH(OR14)—CqH2q—R15 (b-3); —CH2—CH2—(O—CH2—CH2)m—OR14 (b-4); —CH2—CH2—(O—CH2—CH2)m—NR5aR5b (b-5); -a1=a2-a3=a4- is —CH═CH—CH═CH—; —N═CH—CH═CH—; —CH═N—CH═CH—; —CH═CH—N═CH—; —CH═CH—CH═N—; wherein hydrogen atoms in (c-1)-(c-5) may be replaced by certain radicals; R3 is optionally substituted phenyl or a monocyclic or bicyclic aromatic heterocyclic ring system that can be substituted; R21 is halo, hydroxy, amino, carboxyl, C1-6alkyl, C3-7cycloalkyl, arylC1-6alkyl, formyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyloxy, —C(═O)—NR13R14; C1-6alkyloxy, arylC1-6alkyloxy, polyhaloC1-6alkyloxy, amino, mono or di(C1-6alkyl)amino, formylamino, C1-6alkylcarbonylamino, C1-6alkylsulfonylamino, mercapto, C1-6alkylthio, arylthio, aryloxy, arylC1-6alkylthio, C1-6alkylsulfynyl, C1-6alkylsulfonyl, aryl, arylamino, Het1, Het2.

摘要翻译： 式（I）的4-取代的1,5-二氢吡啶并[3,2-b]吲哚-2-酮：N-氧化物，盐，立体异构形式，外消旋混合物，前药，酯和代谢物，其中n 是1，2或3; R 1是氢，氰基，卤素，取代的羰基，甲酰亚胺基，N-羟基 - 甲酰亚胺基，单或二（C 1-4烷基）甲酰亚胺基，Het1或Het2; X是NR2，O，S，SO，SO2; R 2是氢，C 1-10烷基，C 2-10烯基，C 3-7环烷基，其任选被取代; R2是被-COOR4取代的芳基; 或R2是：-CpH2p-CH（OR14）-CqH2q-R15（b-3）; -CH 2 -CH 2 - （O-CH 2 -CH 2）m -OR 14（b-4）; -CH 2 -CH 2 - （O-CH 2 -CH 2）m -NR 5 a R 5b（b-5）; -a1 = a2-a3 = a4-是-CH-CH-CH-CH-; -N-CH-CH-CH-; -CH-N-CH-CH-; -CH-CH-N-CH-; -CH-CH-CH-N-; 其中（c-1） - （c-5）中的氢原子可被某些基团取代; R3是任选取代的苯基或可被取代的单环或双环芳族杂环体系; R 21是卤素，羟基，氨基，羧基，C 1-6烷基，C 3-7环烷基，芳基C 1-6烷基，甲酰基，C 1-6烷基羰基，C 1-6烷氧基羰基，C 1-6烷基羰氧基，-C（-O）-NR 13 R 14; C 1-6烷氧基，芳基C 1-6烷氧基，多卤代C 1-6烷氧基，氨基，一或二（C 1-6烷基）氨基，甲酰氨基，C 1-6烷基羰基氨基，C 1-6烷基磺酰基氨基，巯基，C 1-6烷硫基，芳硫基，芳氧基，芳基C 1-6烷硫基， C 1-6烷基磺酰基，芳基，芳基氨基，Het1，Het2。

公开(公告)号：US20100029635A1

公开(公告)日：2010-02-04

申请号：US12576761

申请日：2009-10-09

申请人： Bart Rudolf Romanie Kesteleyn ,  Sandrine Marie Helene Vendeville ,  Natalie Maria Francisca Kindermans ,  Dominique Louis Nestor Ghislai Surleraux ,  Pierre Jean-Marie Bernard Raboisson ,  Piet Tom Bert Paul Wigerinck ,  Annick Ann Peeters

发明人： Bart Rudolf Romanie Kesteleyn ,  Sandrine Marie Helene Vendeville ,  Natalie Maria Francisca Kindermans ,  Dominique Louis Nestor Ghislai Surleraux ,  Pierre Jean-Marie Bernard Raboisson ,  Piet Tom Bert Paul Wigerinck ,  Annick Ann Peeters

IPC分类号： A61K31/5377 ,  C07D471/04 ,  C07D413/14 ,  C07D401/14 ,  A61K31/437 ,  A61K31/497 ,  A61P31/16

CPC分类号： C07D471/04

摘要： This invention concerns the compounds the N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein X is NR2, O, S, SO, SO2; R1 is hydrogen, cyano, halo, substituted carbonyl, methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; n is 1, 2 or 3; R2 is hydrogen, aryl substituted with a radical —COOR4; or R2 is substituted C1-10alkyl, C2-10alkenyl or C3-7cycloalkyl; or R2 is a radical of formula: —CpH2p—CH(OR14)—CqH2q—R15 (b-3); —CH2—CH2—(O—CH2—CH2)m—OR14 (b-4); —CH2—CH2—(O—CH2—CH2)m—NR5aR5b(b-5) -a1=a2-a3=a4- is —CH═CH—CH═CH—; —N═CH—CH═CH—; —CH═N—CH═CH—; —CH═CH—N═CH—; —CH═CH—CH═N— (c-5); wherein one of the hydrogen atoms in (c-1)-(c-5) is replaced by particular radicals; R3 is nitro, cyano, amino, halo, hydroxy, C1-4alkyloxy, hydroxycarbonyl, substituted carbonyl, methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, N-hydroxy-methanimidamidyl or Het1.

摘要翻译： 本发明涉及N-氧化物，盐，立体异构形式，外消旋混合物，前药，酯和代谢物的化合物，其中X是NR 2，O，S，SO，SO 2; R 1是氢，氰基，卤素，取代的羰基，甲酰亚胺基，N-羟基 - 甲酰亚胺基，单或二（C 1-4烷基）甲酰亚胺基，Het1或Het2; n为1,2或3; R2是氢，被基团-COOR4取代的芳基; 或R 2为取代的C 1-10烷基，C 2-10烯基或C 3-7环烷基; 或R 2是下式的基团：-CpH 2 -p-CH（OR 14）-C≡H2 q-R 15（b-3）; -CH 2 -CH 2 - （O-CH 2 -CH 2）m -OR 14（b-4）; -CH2-CH2-（O-CH2-CH2）m-NR5aR5b（b-5）-a1 = a2-a3 = a4-是-CH-CH-CH-CH-; -N-CH-CH-CH-; -CH-N-CH-CH-; -CH-CH-N-CH-; -CH-CH-CH-N-（c-5）; （c-1） - （c-5）中的一个氢原子被特定基团取代; R3是硝基，氰基，氨基，卤素，羟基，C1-4烷氧基，羟基羰基，取代的羰基，甲酰亚胺基，单或二（C1-4烷基）甲嘧磺酰氨基，N-羟基 - 甲亚胺酰氨基或Het1。

公开(公告)号：US07615639B2

公开(公告)日：2009-11-10

申请号：US11568845

申请日：2005-05-17

申请人： Bart Rudolf Romanie Kesteleyn ,  Pierre Jean-Marie Bernard Raboisson ,  Dominique Louis Nestor Surleraux ,  Geerwin Yvonne Paul Haché ,  Sandrine Marie Helene Vendeville ,  Piet Tom Bert Paul Wigerinck ,  Annick Ann Peeters

发明人： Bart Rudolf Romanie Kesteleyn ,  Pierre Jean-Marie Bernard Raboisson ,  Dominique Louis Nestor Surleraux ,  Geerwin Yvonne Paul Haché ,  Sandrine Marie Helene Vendeville ,  Piet Tom Bert Paul Wigerinck ,  Annick Ann Peeters

IPC分类号： C07D471/00

CPC分类号： C07D471/04

摘要： 1-heterocyclyl-1,5-dihydro-pyrido[3,2-b]indol-2-ones of formula (I): the N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein n is 1, 2 or 3; R1 is hydrogen, cyano, halo, substituted carbonyl, methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; X is NR2, O, S, SO, SO2; R2 is hydrogen, C1-10alkyl, C2-10alkenyl, C3-7cycloalkyl, which are optionally substituted; R2 is aryl substituted with —COOR4; or R2 is: —CpH2p—CH(OR14)—CqH2q—R15   (b-3); —CH2—CH2—(O—CH2—CH2)m—OR14   (b-4); —CH2—CH2—(O—CH2—CH2)m—NR5aR5b (b-5); -a1=a2-a3=a4- is —CH═CH—CH═CH—; —N═CH—CH═CH—; —CH═N—CH═CH—; —CH═CH—N═CH—; —CH═CH—CH═N—; wherein hydrogen atoms in (c-1)-(c-5) may be replaced by certain radicals; R3 is a monocyclic or bicyclic aromatic heterocyclic ring system that can be substituted.

摘要翻译： 式（I）的1-杂环基-1,5-二氢 - 吡啶并[3,2-b]吲哚-2-酮：N-氧化物，盐，立体异构形式，外消旋混合物，前药，酯和代谢物，其中 n为1,2或3; R 1是氢，氰基，卤素，取代的羰基，甲酰亚胺基，N-羟基 - 甲酰亚胺基，单或二（C 1-4烷基）甲酰亚胺基，Het1或Het2; X是NR2，O，S，SO，SO2; R 2是氢，C 1-10烷基，C 2-10烯基，C 3-7环烷基，其任选被取代; R2是被-COOR4取代的芳基; 或R2是：-CpH2p-CH（OR14）-CqH2q-R15（b-3）; -CH 2 -CH 2 - （O-CH 2 -CH 2）m -OR 14（b-4）; -CH 2 -CH 2 - （O-CH 2 -CH 2）m -NR 5 a R 5b（b-5）; -a1 = a2-a3 = a4-是-CH-CH-CH-CH-; -N-CH-CH-CH-; -CH-N-CH-CH-; -CH-CH-N-CH-; -CH-CH-CH-N-; 其中（c-1） - （c-5）中的氢原子可被某些基团取代; R3是可被取代的单环或双环芳族杂环体系。