公开(公告)号：US06833375B2

公开(公告)日：2004-12-21

申请号：US10238686

申请日：2002-09-10

申请人： Marc Gaston Venet ,  Dominique Jean-Pierre Mabire ,  Jean Fernand Armand Lacrampe ,  Gerard Charles Sanz

发明人： Marc Gaston Venet ,  Dominique Jean-Pierre Mabire ,  Jean Fernand Armand Lacrampe ,  Gerard Charles Sanz

IPC分类号： C07D41710

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D487/04 ,  C07D513/04

摘要： The present invention is concerned with compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein R1 is hydrogen, hydroxy, C1-6alkyl or aryl; R2 is hydrogen; optionally substituted C1-12alkyl; C3-7cycloalkyl; C2-8alkenyl, optionally substituted pyrrolidinyl or aryl; R3 is hydrogen, optionally substituted C1-6alkyl or aryl; Het is an optionally substituted unsaturated heterocycle selected from imidazolyl, triazolyl, tetrazolyl and pyridinyl; is an optionally substituted unsaturated mono- or bicyclic heterocycle; and aryl is optionally substituted phenyl. The present invention also relates to processes for their preparation and compositions comprising said new compounds, as well as their use as a medicine.

摘要翻译： 本发明涉及配制N-氧化物的化合物，其药学上可接受的加成盐和立体化学异构形式，其中R 1是氢，羟基，C 1-6烷基或芳基; R 2是氢; 任选取代的C 1-12烷基; C 3-7环烷基; C 2-8烯基，任选取代的吡咯烷基或芳基; R 3是氢，任选取代的C 1-6烷基或芳基; Het是选自咪唑基，三唑基，四唑基和吡啶基的任选取代的不饱和杂环;是任选取代的不饱和单环或双环杂环; 并且芳基是任选取代的苯基。 本发明还涉及其制备方法和包含所述新化合物的组合物，以及它们作为药物的用途。

公开(公告)号：US07378433B2

公开(公告)日：2008-05-27

申请号：US11639043

申请日：2006-12-13

申请人： Marc Gaston Venet ,  Dominique Jean-Pierre Mabire ,  Jean Fernand Armand Lacrampe ,  Gerard Charles Sanz

发明人： Marc Gaston Venet ,  Dominique Jean-Pierre Mabire ,  Jean Fernand Armand Lacrampe ,  Gerard Charles Sanz

IPC分类号： A61K31/425 ,  C07D257/04

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D487/04 ,  C07D513/04

摘要： The present invention is concerned with compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein R1 is hydrogen, hydroxy, C1-6alkyl or aryl; R2 is hydrogen; optionally substituted C1-12alkyl; C3-7cycloalkyl; C2-8alkenyl, optionally substituted pyrrolidinyl or aryl; R3 is hydrogen, optionally substituted C1-6alkyl or aryl; Het is an optionally substituted unsaturated heterocycle selected from imidazolyl, triazolyl, tetrazolyl and pyridinyl; is an optionally substituted unsaturated mono- or bicyclic heterocycle; and aryl is optionally substituted phenyl. The present invention also relates to processes for their preparation and compositions comprising said new compounds, as well as their use as a medicine.

摘要翻译： 本发明涉及式I化合物的N-氧化物，其药学上可接受的加成盐和立体化学异构形式，其中R 1是氢，羟基，C 1-6 - 烷基或芳基; R 2是氢; 任选取代的C 1-12烷基; C 3-7环烷基; C 2-8链烯基，任选取代的吡咯烷基或芳基; R 3是氢，任选取代的C 1-6烷基或芳基; Het是选自咪唑基，三唑基，四唑基和吡啶基的任选取代的不饱和杂环; 是任选取代的不饱和单环或双环杂环; 并且芳基是任选取代的苯基。 本发明还涉及其制备方法和包含所述新化合物的组合物，以及它们作为药物的用途。

公开(公告)号：US07355051B2

公开(公告)日：2008-04-08

申请号：US10596519

申请日：2004-12-20

申请人： Jean-François Bonfanti ,  Koenraad Jozef Lodewijk Andries ,  Frans Eduard Janssens ,  François Maria Sommen ,  Jerôme Emile Georges Guillemont ,  Jean Fernand Armand Lacrampe

发明人： Jean-François Bonfanti ,  Koenraad Jozef Lodewijk Andries ,  Frans Eduard Janssens ,  François Maria Sommen ,  Jerôme Emile Georges Guillemont ,  Jean Fernand Armand Lacrampe

IPC分类号： C07D401/106

CPC分类号： C07D401/14 ,  C07D417/14

摘要： The present invention concerns piperidine-amino-benzimidazoles having inhibitory activity on the replication of the respiratory syncytial virus and having the formula their prodrugs, N-oxides, addition salts, quaternary amines, metal complexes and stereochemically isomeric forms wherein Q is C1−6alkyl optionally substituted with trifluoromethyl, C3-7cycloalkyl, Ar2, hydroxy, C1−4alkoxy, C1−4alkylthio, Ar2-oxy-, Ar2-thio-, Ar2(CH2)noxy, Ar2(CH2)nthio, hydroxycarbonyl, aminocarbonyl, C1−4alkyl-carbonyl, Ar2carbonyl, C1−4alkoxycarbonyl, Ar2(CH2)ncarbonyl, aminocarbonyloxy, C1−4alkylcarbonyloxy, Ar2carbonyloxy, Ar2(CH2)ncarbonyloxy, C1−4alkoxy-carbonyl(CH2)noxy, mono- or di(C1−4alkyl)aminocarbonyl, mono- or di(C1−4alkyl)-aminocarbonyloxy, aminosulfonyl, mono- or di(C1−4alkyl)aminosulfonyl or a heterocycles selected from the group consisting of pyrrolidinyl, pyrrolyl, dihydropyrrolyl, imidazolyl, triazolyl, piperidinyl, homopiperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxothiomorpholinyl, pyridyl and tetrahydropyridyl, wherein each of said heterocycle may optionally be substituted with oxo or C1−6alkyl; G is a direct bond or optionally substituted C1-10alkanediyl; R1 is Ar1 or a monocyclic or bicyclic heterocycle; one of R2a and R3a is C1−6alkyl and the other one of R2a and R3a is hydrogen; in case R2a is different from hydrogen then R2b is hydrogen or C1−6alkyl, and R3b is hydrogen; in case R3a is different from hydrogen then R3b is hydrogen or C1−6alkyl, and R2b is hydrogen; t is 1, 2 or 3; Ar1 is phenyl or substituted phenyl; and Ar2 is phenyl or substituted phenyl. It further concerns their preparation and compositions comprising them, as well as their use as a medicine.

公开(公告)号：US06803364B1

公开(公告)日：2004-10-12

申请号：US09868384

申请日：2001-08-29

申请人： Eddy Jean Edgard Freyne ,  Frederik Dirk Deroose ,  Jean Fernand Armand Lacrampe ,  Werner Constant Johan Embrechts ,  Jerome Michel Claude Fortin

发明人： Eddy Jean Edgard Freyne ,  Frederik Dirk Deroose ,  Jean Fernand Armand Lacrampe ,  Werner Constant Johan Embrechts ,  Jerome Michel Claude Fortin

IPC分类号： C07D25306

CPC分类号： C07D253/075 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14

摘要： The present invention is concerned with the compounds of formula (I), a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein p is 0 to 4; q is 0 to 5; X is O, S, NR3 or a direct bond; or —X—R2 is CN; R1 is H, OH, halo, NH2, mono- or di(C1-4alkyl)NH2, C1-6alkyl, C1-6alkylO, C3-7cycloalkyl, aryl, arylC1-6alkyl, NH2C1-4akyl, mono- or di(C1-4alkyl)NH2C1-4akyl or mono- or di(C1-4alkyl)NH2C1-4alkylNH2; R2 is aryl, Het1, optionally substituted C3-7cycloalkyl, optionally substituted C1-6alkyl; R3 is H or C1-4alkyl; R4 and R5 are —C(═O)—Z—R14, C1-6alkyl, halo, polyhaloC1-6alkyl, OH, mercapto, C1-6alkylO, C1-6alkylthio, C1-6alkylC(═O)O, aryl, cyano, nitro, Het3, R6, NR7R8 or C1-4alkyl substituted with —C(═O)—Z—R14, Het3, R6 or NR7R8; Z is O, S, NH, —CH2O or —CH2—S—; R14 is H, C1-20acyl, optionally substituted C1-20alkyl, optionally substituted C3-20alkenyl, C3-20alkynyl, C3-7cycloalkyl, polyhaloC1-20alkyl, Het5, phenyl; or R14 is an oxygen containing radical; aryl is optionally substituted phenyl; Het1, Het2, Het3 and Het5 are optionally substituted heterocycles; Het4 is a monocyclic heterocycle; provided however that R2 is other than NH2C(═O), C1-6alkylOC(═O)C1-6alkyl; and R11 is other than COOH, C1-4alkylOC(═O), NH2C(═O), C1-4alkylNH2C(═O), OHC1-4alkylNH2C(═O), C1-4alkylC(═O)NH2C(═O), C3-7cycloalkylNH2C(═O); and R7, R8, R9, R10, R12, R13, R15 and R16 are other than C1-4alkylC(═O)OC1-4alkylC(═O), OHC1-4alkylC(═O); and Het3 is other than a monocyclic heterocycle substituted with COOH or C1-4alkylOC(═O); and the compounds of formula (I) contain at least one —C(═O)—Z—R14 moiety: to processes for their preparation and compositions comprising them. It further relates to their use as a medicine.

摘要翻译： 本发明涉及式（I）化合物，N-氧化物，药学上可接受的加成盐，季胺或其立体化学异构形式，其中p为0至4; q为0〜5; X是O，S，NR 3或直接键; 或-X-R 2为CN; R 1是H，OH，卤素，NH 2，单或二（C 1-4烷基）NH 2，C 1-6烷基，C 1-6烷基O，C 3-7环烷基，芳基，芳基C 1-6烷基，NH 2 C 1-4烷基，单或二 （C 1-4烷基）NH 2 C 1-4芳基或单或二（C 1-4烷基）NH 2 C 1-4烷基NH 2; R 2是芳基，Het 1，任选取代的C 3-7环烷基，任选取代的C 1-6烷基; R 3是H或C 1-4烷基; R 4和R 5是-C（= O）-ZR 14，C 1-6烷基，卤素，多卤代C 1-6烷基，OH，巯基，C 1-6烷基O，C 1-6烷硫基，C 1-6烷基C（= O ）O，芳基，氰基，硝基，Het 3，R 6，NR 7 R 8或被-C（= O）-ZR 14，Het 3取代的C 1-4烷基， R 6或NR 7 R 8; Z是O，S，NH，-CH 2 O或-CH 2 -S-; R 14是H，C 1-20酰基，任选取代的C 1-20烷基，任选取代的C 3-20烯基，C 3-20炔基，C 3-7环烷基，多卤代C 1-20烷基，Het 5，苯基; 或R 14是含氧基团; 芳基是任选取代的苯基; Het 1，Het 2，Het 3和Het 5是任选取代的杂环; Het 4是单环杂环; 但是R 2不是NH

公开(公告)号：US06498158B1

公开(公告)日：2002-12-24

申请号：US09856626

申请日：2001-05-22

申请人： Jean Fernand Armand Lacrampe ,  Yannick Ligny ,  Eddy Jean Edgard Freyne ,  Frederik Dirk Deroose

发明人： Jean Fernand Armand Lacrampe ,  Yannick Ligny ,  Eddy Jean Edgard Freyne ,  Frederik Dirk Deroose

IPC分类号： C07D253075

CPC分类号： C07D253/075 ,  C07D405/10 ,  C07D413/10 ,  C07D413/14 ,  C07D417/10 ,  C07D417/14

摘要： The present invention is concerned with the compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein p is 0 to 3; q is 0 to 4; —A—B— represents —(CH2)r—, —(CH2)t—O—, —(CH2)t—S(═O)u— or —(CH2)t—NR3—; r is 2 to 4; t is 1 to 3; u is 0 to 2; X1 is O, S, NR3 or a direct bond; R1 and R4 are C1-6alkyl, halo, polyhaloC1-6alkyl, hydroxy, mercapto, C1-6alkyloxy, C1-6alkylthio, C1-6alkylcarbonyloxy, aryl, cyano, nitro, Het3, R6, NR7R8 or substituted C1-4alkyl; R2 is aryl, Het1, C3-7cycloalkyl, cyano, optionally substituted C1-6alkyl, —C(═Q)—X2—R15; R3 is hydrogen or C1-4alkyl; R15 is hydrogen, optionally substituted C1-6alkyl, C3-7cycloalkyl, aryl; where X2 is a direct bond, R15 may also be halo or Het1; where X2 is NR5, R15 may also be hydroxy; where X2 is C(═O)—NH—NH or NH—NH—C(═O), R15 may be replaced by R11; Q is O, S or NR3; X2 is O, S, NR5, C(═O)—NH—NH, NH—NH—C(═O) or a direct bond; R5 is hydrogen, C1-6alkyl, C1-6alkyloxy or arylC1-6alkyl; R6 is a sulfonyl or sulfinyl derivative; R7 and R8 are independently hydrogen, optionally substituted C1-4alkyl, aryl, a carbonyl containing moiety, C3-7cycloalkyl, —Y-C1-4alkanediyl-C(═O)—O—R14, Het3 and R6; R11 is hydroxy, mercapto, cyano, nitro, halo, trihalomethyl, C1-4alkyloxy, formyl, trihaloC1-4alkylsulfonyloxy, R6, NR7R8, C(═O)NR7R8, C1-4alkanediyl-C(═O)—O—R14, —C(═O)—O—R14, —Y-C1-4alkanediyl-C(═0)—O—R14, aryl, aryloxy, arylcarbonyl, C3-7cycloalkyl, C3-7cycloalkyloxy, phthalimide-2-yl, Het3, Het4 and C(═O)Het3; aryl is optionally substituted phenyl; Het1, Het2, Het3 and Het4 are optionally substituted heterocycles; to processes for their preparation and compositions comprising them. It further relates to their use as a medicine.

摘要翻译： 本发明涉及配制N-氧化物的化合物，其药学上可接受的加成盐和立体化学异构形式，其中p为0-3; q为0〜4; -A-B-表示 - （CH 2）r - ， - （CH 2）t -O-， - （CH 2）t -S（= O）u - 或 - （CH 2）t -NR 3 - ; r为2〜4; t为1〜3; 你是0到2; X1是O，S，NR3或直接键; R 1和R 4是C 1-6烷基，卤素，多卤代C 1-6烷基，羟基，巯基，C 1-6烷氧基，C 1-6烷硫基，C 1-6烷基羰氧基，芳基，氰基，硝基，Het 3，R 6，NR 7 R 8或取代的C 1-4烷基; R 2是芳基，Het 1，C 3-7环烷基，氰基，任选取代的C 1-6烷基，-C（= Q）-X 2 -R 15; R3是氢或C1-4烷基; R 15是氢，任选取代的C 1-6烷基，C 3-7环烷基，芳基; 其中X2是直接键，R15也可以是卤素或Het1; 其中X2是NR5，R15也可以是羟基; 其中X 2是C（= O）-NH-NH或NH-NH-C（= O），R 15可以被R 11取代; Q是O，S或NR 3; X2是O，S，NR5，C（= O）-NH-NH，NH-NH-C（= O）或直接键; R5是氢，C1-6烷基，C1-6烷氧基或芳基C1-6烷基; R6是磺酰基或亚磺酰基衍生物; R 7和R 8独立地为氢，任选取代的C 1-4烷基，芳基，含羰基部分，C 3-7环烷基，-Y-C 1-4烷二基-C（= O）-O-R 14，Het 3