公开(公告)号：US20100183552A1

公开(公告)日：2010-07-22

申请号：US11993109

申请日：2006-06-20

申请人： Jean-François Bonfanti ,  Philippe Muller ,  Jérôme Michel Claude Fortin ,  Frédéric Marc Maurice Doublet

发明人： Jean-François Bonfanti ,  Philippe Muller ,  Jérôme Michel Claude Fortin ,  Frédéric Marc Maurice Doublet

IPC分类号： A61K38/21 ,  A61K38/19 ,  A61P31/12 ,  C07D471/04 ,  A61K31/437 ,  C07D413/14 ,  A61K31/5377

CPC分类号： C07D471/04 ,  C07D401/14

摘要： Inhibitors of RSV replication of formula (I) which can be represented by formula (I) the salts and stereochemically isomeric forms thereof, wherein R is a radical of formula Q is hydrogen or C1-6alkyl optionally substituted with a heterocycle or Q is C1-6alkyl substituted with both a radical —OR4 and a heterocycle; Alk is C1-6alkanediyl; X is O or S; -a1=a2-a3=a4- is —N═CH—CH═CH—, —CH═N—CH═CH—, —CH═CH—N═CH— or —CH═CH—CH═N—; R1 is Ar or a heterocycle; R2 is hydrogen, C1-6alkyl, substituted C1-6alkyl, C3-7cycloalkyl; R3 is hydrogen, C1-6alkyl, cyano, aminocarbonyl, polyhaloC1-6alkyl, C2-6alkenyl or C2-6alkynyl; R4 is hydrogen or C1-6alkyl; Ar is phenyl or substituted phenyl; Het is a heterocycle; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I).

摘要翻译： 式（I）的RSV复制抑制剂，其可以由式（I）表示其盐和立体化学异构形式，其中R是式Q的基团是氢或任选被杂环取代的C 1-6烷基或Q是C1- 被烷基和-OR4基团取代的6个烷基; Alk是C1-6烷二基; X是O或S; -a1 = a2-a3 = a4-是-N = CH-CH = CH-，-CH = N-CH = CH-，-CH = CH-N = CH-或-CH = CH-CH = N- R1是Ar或杂环; R 2是氢，C 1-6烷基，取代的C 1-6烷基，C 3-7环烷基; R3是氢，C1-6烷基，氰基，氨基羰基，多卤代C 1-6烷基，C 2-6烯基或C 2-6炔基; R4是氢或C1-6烷基; Ar是苯基或取代的苯基; Het是杂环; 含有化合物（I）的药物组合物和制备化合物（I）的方法。

公开(公告)号：US08278455B2

公开(公告)日：2012-10-02

申请号：US12253450

申请日：2008-10-17

申请人： Jean-François Bonfanti ,  Koenraad Jozef Lodewijk Andries ,  Jérôme Michel Claude Fortin ,  Philippe Muller ,  Frédéric Marc Maurice Doublet ,  Christophe Meyer ,  Rudy Edmond Willebrords ,  Tom Valerius Josepha Gevers ,  Philip Maria Martha Bern Timmerman

发明人： Jean-François Bonfanti ,  Koenraad Jozef Lodewijk Andries ,  Jérôme Michel Claude Fortin ,  Philippe Muller ,  Frédéric Marc Maurice Doublet ,  Christophe Meyer ,  Rudy Edmond Willebrords ,  Tom Valerius Josepha Gevers ,  Philip Maria Martha Bern Timmerman

IPC分类号： A61K31/4439 ,  C07D401/06

CPC分类号： C07D401/06 ,  C07D401/14 ,  C07D405/14

摘要： The present invention concerns 5- or 6-substituted-benzimidazole derivatives having inhibitory activity on the replication of the respiratory syncytial virus and having the formula a prodrug, N-oxide, addition salt, quaternary amine, metal complex or stereochemically isomeric form thereof wherein Q is Ar2, R6, pyrrolidinyl substituted with R6, piperidinyl substituted with R6 or homopiperidinyl substituted with R6, G is a direct bond or optionally substituted C1-10alkanediyl; R1 is Ar1 or a monocyclic or bicyclic heterocycle; one of R2a and R2b is cyanoC1-6alkyl, cyanoC2-6alkenyl, Ar3C1-6alkyl, Het1C1-6alkyl, N(R8aR8b)C1-6alkyl, Ar3C2-6alkenyl, Het1C2-6alkenyl, Ar3aminoC1-6alkyl, Het1aminoC1-6alkyl, Ar3thioC1-6alkyl, Het1thioC1-6alkyl, Ar3sulfonylC1-6alkyl, Het1sulfonylC1-6alkyl, Ar3aminocarbonyl, Het1aminocarbonyl, Ar3(CH2)namino-carbonyl, Het1(CH2)naminocarbonyl, Ar3carbonylamino, Het1carbonylamino, Ar3(CH2)ncarbonylamino, Het1(CH2)ncarbonylamino, and the other one of R2a and R2b is hydrogen; in case R2a is hydrogen, then R3 is hydrogen; in case R2b is hydrogen, the R3 is hydrogen or C1-6alkyl. It further concerns their preparation and compositions comprising them, as well as their use as a medicine.

摘要翻译： 本发明涉及对呼吸道合胞病毒复制具有抑制活性的5-或6-取代苯并咪唑衍生物，其具有前药，N-氧化物，加成盐，季胺，金属络合物或其立体化学异构形式，其中Q 是Ar 2，R 6，被R 6取代的吡咯烷基，被R 6取代的哌啶基或被R 6取代的高哌啶基，G是直接键或任意取代的C 1-10烷二基; R1是Ar1或单环或双环杂环; R2a和R2b之一是氰基C 1-6烷基，氰基C 2-6烯基，Ar 3 C 1-6烷基，Het 1 C 1-6烷基，N（R 8 a R 8 b）C 1-6烷基，Ar 3 C 2-6烯基，Het 1 C 2-6烯基，Ar 3氨基C 1-6烷基，Het 1氨基C 1-6烷基，Ar 3硫代C 1-6烷基， （CH 2）n氨基 - 羰基，Het 1（CH 2）n氨基羰基，Ar 3羰基氨基，Het 1羰基氨基，Ar 3（CH 2）n - 羰基氨基，Het 1（CH 2）n - 羰基氨基，和另一个（CH 2）n C 1 -C 6烷基， R2a和R2b是氢; 在R2a为氢的情况下，R3为氢; 在R2b为氢的情况下，R3为氢或C1-6烷基。 它还涉及它们的制备方法和包含它们的组合物，以及它们作为药物的用途。

公开(公告)号：US07884215B2

公开(公告)日：2011-02-08

申请号：US11993136

申请日：2006-06-20

申请人： Jean-François Bonfanti ,  Philippe Muller ,  Jérôme Michel Claude Fortin ,  Frédéric Marc Maurice Doublet

发明人： Jean-François Bonfanti ,  Philippe Muller ,  Jérôme Michel Claude Fortin ,  Frédéric Marc Maurice Doublet

IPC分类号： C07D295/00

CPC分类号： C07D401/06 ,  C07D235/30

摘要： Inhibitors of RSV replication of formula (I) the addition salts and stereochemically isomeric forms thereof, wherein Q is hydrogen, C1-6alkyl optionally substituted with a heterocycle or Q is C1-6alkyl substituted with both —OR4 and a heterocycle; wherein said heterocycle is oxazolidine, thiazolidine, 1-oxo-thiazolidine, 1,1-dioxothiazolidine, morpholinyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxothiomorpholinyl, hexahydrooxazepine, hexahydro-thiazepine, 1-oxo-hexahydrothiazepine, 1,1-dioxo-hexahydrothiazepine, pyrrolidine, piperidine, homopiperidine, piperazine; which heterocyle may be substituted with 1-2 substituents; each Alk is C1-6alkanediyl; R1 is Ar2 or optionally substituted piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, furanyl, tetrahydro-furanyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, isothiazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, quinolinyl, quinoxalinyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, pyridopyridyl, naphthiridinyl, 1H-imidazo[4,5-b]pyridinyl, 3H-imidazo[4,5-b]pyridinyl, imidazo[1,2-a]pyridinyl or 2,3-dihydro-1,4-dioxino[2,3-b]pyridyl; R3 is hydroxyC1-6alkyl, C1-6alkoxyC1-6alkyl, cyanoC1-6alkyl, aminocarbonyl-C1-6-alkyl, mono- or di(C1-6alkyl)aminocarbonyl-C1-6-alkyl, carboxyl-C1-6-alkyl, C1-6alkoxycarbonyl-C1-6alkyl; R2 is hydrogen or C1-6alkyl; R3 and R4 are hydrogen, C1-6alkyl, Ar2, Ar2C1-6alkyl, C1-6alkylcarbonyl, Ar2carbonyl, Ar2C1-6alkylcarbonyl, C1-6alkylsulfonyl, aminosulfonyl, Ar1sulfonyl, Ar1C1-6alkylsulfonyl, C1-6alkyloxyC1-6alkyl, aminoC1-6alkyl, mono- or di(C1-6alkyl)-aminoC1-6alkyl, hydroxyC1-6alkyl, aminocarbonylC1-6alkyl, C1-4alkyloxycarbonyl-C1-6alkyl, hydroxycarbonylC1-6alkyl, aminosulfonylC1-6alkyl, Het, Het-C1-6alkyl, Het-carbonyl, Het-sulfonyl, HetC1-6alkylsulfonyl, Het-C1-6alkylcarbonyl; Het is an optionally substituted heterocycle; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I).

公开(公告)号：US08178694B2

公开(公告)日：2012-05-15

申请号：US11993126

申请日：2006-06-20

申请人： Jean-François Bonfanti ,  Philippe Muller ,  Jérôme Michel Claude Fortin ,  Frédéric Marc Maurice Doublet

发明人： Jean-François Bonfanti ,  Philippe Muller ,  Jérôme Michel Claude Fortin ,  Frédéric Marc Maurice Doublet

IPC分类号： A61K31/5377 ,  C07D413/14

CPC分类号： C07D401/06 ,  C07D401/14

摘要： Heterocyclylaminoalkyl Substituted Benzimidazoles Inhibitors of RSV replication of formula (I): The salts and stereochemically isomeric forms thereof, wherein Q is hydrogen, C1-6alkyl optionally substituted with a heterocycle or Q is C1-6alkyl substituted with both —OR4 and a heterocycle; wherein said heterocycle is oxazolidine, thiazolidine, 1-oxo-thiazolidine, 1,1-dioxothiazolidine, morpholinyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxothiomorpholinyl, hexahydrooxazepine, hexahydrothiazepine, 1-oxo-hexahydrothiazepine, 1,1-dioxo-hexahydrothiazepine, pyrrolidine, piperidine, homopiperidine, piperazine; which heterocyle may be substituted with 1-2 substituents; each Alk is C1-6alkanediyl; R1 is Ar or optionally substituted piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, furanyl, tetrahydrofuranyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, isothiazolyl, pyrazolyl, isoxazo lyl, oxadiazolyl, quinolinyl, quinoxalinyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, pyridopyridyl, naphthiridinyl, 1H-imidazo[4,5-b]pyridinyl, 3H-imidazo[4,5-b]pyridinyl, imidazo[1,2-a]pyridinyl or 2,3-dihydro-1,4-dioxino[2,3-b]pyridyl; R3 is hydroxyC1-6alkyl, C1-6alkoxyC1-6alkyl, cyanoC1-6alkyl, aminocarbonyl-C1-6-alkyl, mono- or di(C1-6alkyl)aminocarbonyl-C1-6-alkyl, carboxyl-C1-6-alkyl, C1-6alkoxycarbonyl-C1-6 alkyl; R2, R4 and R5 are hydrogen or C1-6alkyl; Het is pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, furanyl, tetrahydrofuranyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, isothiazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, quinolinyl, quinoxalinyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazo lyl, benzthiazolyl, pyridopyridyl, naphthiridinyl, 1H-imidazo[4,5-b]-pyridinyl, 3H-imidazo[4,5-b]pyridinyl, imidazo[1,2-a]pyridinyl and 2,3-dihydro-1,4-dioxino[2,3-b]pyridyl; Ar is optionally substituted phenyl; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I).

公开(公告)号：US08034835B2

公开(公告)日：2011-10-11

申请号：US11993109

申请日：2006-06-20

申请人： Jean-François Bonfanti ,  Philippe Muller ,  Jérôme Michel Claude Fortin ,  Frédéric Marc Maurice Doublet

发明人： Jean-François Bonfanti ,  Philippe Muller ,  Jérôme Michel Claude Fortin ,  Frédéric Marc Maurice Doublet

IPC分类号： C07D235/04 ,  C07D403/02 ,  A01N43/52 ,  A61K31/415

CPC分类号： C07D471/04 ,  C07D401/14

摘要： Inhibitors of RSV replication of formula (I) which can be represented by formula (I) the salts and stereochemically isomeric forms thereof, wherein R is a radical of formula Q is hydrogen or C1-6alkyl optionally substituted with a heterocycle or Q is C1-6alkyl substituted with both a radical —OR4 and a heterocycle; Alk is C1-6alkanediyl; X is O or S; -a1=a2-a3=a4- is —N═CH—CH═CH—, —CH═N—CH═CH—, —CH═CH—N═CH— or —CH═CH—CH═N—; R1 is Ar or a heterocycle; R2 is hydrogen, C1-6alkyl, substituted C1-6alkyl, C3-7cycloalkyl; R3 is hydrogen, C1-6alkyl, cyano, aminocarbonyl, polyhaloC1-6alkyl, C2-6alkenyl or C2-6alkynyl; R4 is hydrogen or C1-6alkyl; Ar is phenyl or substituted phenyl; Het is a heterocycle; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I).

摘要翻译： 式（I）的RSV复制抑制剂，其可以由式（I）表示其盐和立体化学异构形式，其中R是式Q的基团是氢或任选被杂环取代的C 1-6烷基或Q是C1- 被烷基和-OR4基团取代的6个烷基; Alk是C1-6烷二基; X是O或S; -a1 = a2-a3 = a4-是-N = CH-CH = CH-，-CH = N-CH = CH-，-CH = CH-N = CH-或-CH = CH-CH = N- R1是Ar或杂环; R 2是氢，C 1-6烷基，取代的C 1-6烷基，C 3-7环烷基; R3是氢，C1-6烷基，氰基，氨基羰基，多卤代C 1-6烷基，C 2-6烯基或C 2-6炔基; R4是氢或C1-6烷基; Ar是苯基或取代的苯基; Het是杂环; 含有化合物（I）的药物组合物和制备化合物（I）的方法。

公开(公告)号：US07449463B2

公开(公告)日：2008-11-11

申请号：US10563691

申请日：2004-12-20

申请人： Jean-François Bonfanti ,  Koenraad Jozef Lodewijk Andries ,  Jérôme Michel Claude Fortin ,  Philippe Muller ,  Frédéric Marc Maurice Doublet ,  Christophe Meyer ,  Rudy Edmond Willebrords ,  Tom Valerius Josepha Gevers ,  Philip Maria Martha Bern Timmerman

发明人： Jean-François Bonfanti ,  Koenraad Jozef Lodewijk Andries ,  Jérôme Michel Claude Fortin ,  Philippe Muller ,  Frédéric Marc Maurice Doublet ,  Christophe Meyer ,  Rudy Edmond Willebrords ,  Tom Valerius Josepha Gevers ,  Philip Maria Martha Bern Timmerman

IPC分类号： A61K31/535 ,  C07D413/00

CPC分类号： C07D413/12 ,  C07D401/06 ,  C07D401/14 ,  C07D413/14

摘要： The present invention concerns morpholinyl containing benzimidazoles having inhibitory activity on the replication of the respiratory syncytial virus and having the formula a prodrug, N-oxide, addition salt, quaternary amine, metal complex or stereochemically isomeric form thereof wherein G is a direct bond or optionally substituted C1-10alkanediyl; R1 is Ar1 or a monocyclic or bicyclic heterocycle Q is R7, pyrrolidinyl substituted with R7, piperidinyl substituted with R7 or homopiperidinyl substituted with R7; one of R2a and R3a is selected from halo, optionally mono- or polysubstituted C1-6alkyl, optionally mono- or polysubstituted C2-6alkenyl, nitro, hydroxy, Ar2, N(R4aR4b), N(R4aR4b)sulfonyl, N(R4aR4b)carbonyl, C1-6alkyloxy, Ar2oxy, Ar2C1-6alkyloxy, carboxyl, C1-6alkyloxycarbonyl, or —C(=Z)Ar2; and the other one of R2a and R3a is hydrogen; in case R2a is different from hydrogen then R2b is hydrogen, C1-6alkyl or halogen and R3b is hydrogen; in case R3a is different from hydrogen then R3b is hydrogen, C1-6alkyl or halogen and R2b is hydrogen. It further concerns the preparation thereof and compositions comprising these compounds, as well as the use thereof as a medicine.

公开(公告)号：US20100092426A1

公开(公告)日：2010-04-15

申请号：US11993136

申请日：2006-06-20

申请人： Jean-Francois Bonfanti ,  Philippe Muller ,  Jérôme Michel Claude Fortin ,  Frédéric Marc Maurice Doublet

发明人： Jean-Francois Bonfanti ,  Philippe Muller ,  Jérôme Michel Claude Fortin ,  Frédéric Marc Maurice Doublet

IPC分类号： C07D401/06 ,  C07D413/14 ,  A61K31/5377 ,  A61K31/4439 ,  A61P31/12 ,  A61K38/21 ,  A61K38/19

CPC分类号： C07D401/06 ,  C07D235/30

摘要： Inhibitors of RSV replication of formula (I) the addition salts and stereochemically isomeric forms thereof, wherein Q is hydrogen, C1-6alkyl optionally substituted with a heterocycle or Q is C1-6alkyl substituted with both —OR4 and a heterocycle; wherein said heterocycle is oxazolidine, thiazolidine, 1-oxo-thiazolidine, 1,1-dioxothiazolidine, morpholinyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxothiomorpholinyl, hexahydrooxazepine, hexahydro-thiazepine, 1-oxo-hexahydrothiazepine, 1,1-dioxo-hexahydrothiazepine, pyrrolidine, piperidine, homopiperidine, piperazine; which heterocyle may be substituted with 1-2 substituents; each Alk is C1-6alkanediyl; R1 is Ar2 or optionally substituted piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, furanyl, tetrahydro-furanyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, isothiazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, quinolinyl, quinoxalinyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, pyridopyridyl, naphthiridinyl, 1H-imidazo[4,5-b]pyridinyl, 3H-imidazo[4,5-b]pyridinyl, imidazo[1,2-a]pyridinyl or 2,3-dihydro-1,4-dioxino[2,3-b]pyridyl; R3 is hydroxyC1-6alkyl, C1-6alkoxyC1-6alkyl, cyanoC1-6alkyl, aminocarbonyl-C1-6-alkyl, mono- or di(C1-6alkyl)aminocarbonyl-C1-6-alkyl, carboxyl-C1-6-alkyl, C1-6alkoxycarbonyl-C1-6alkyl; R2 is hydrogen or C1-6alkyl; R3 and R4 are hydrogen, C1-6alkyl, Ar2, Ar2C1-6alkyl, C1-6alkylcarbonyl, Ar2carbonyl, Ar2C1-6alkylcarbonyl, C1-6alkylsulfonyl, aminosulfonyl, Ar1sulfonyl, Ar1C1-6alkylsulfonyl, C1-6alkyloxyC1-6alkyl, aminoC1-6alkyl, mono- or di(C1-6alkyl)-aminoC1-6alkyl, hydroxyC1-6alkyl, aminocarbonylC1-6alkyl, C1-4alkyloxycarbonyl-C1-6alkyl, hydroxycarbonylC1-6alkyl, aminosulfonylC1-6alkyl, Het, Het-C1-6alkyl, Het-carbonyl, Het-sulfonyl, HetC1-6alkylsulfonyl, Het-C1-6alkylcarbonyl; Het is an optionally substituted heterocycle; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I).

公开(公告)号：US08883837B2

公开(公告)日：2014-11-11

申请号：US12140686

申请日：2008-06-17

申请人： Jean-Francois Bonfanti ,  Koenraad Jozef Lodewijk Andries ,  Jérôme Michel Claude Fortin ,  Philippe Muller ,  Frédéric Marc Maurice Doublet ,  Christophe Meyer ,  Rudy Edmond Willebrords ,  Tom Valerius Josepha Gevers ,  Philip Maria Martha Bern Timmerman

发明人： Jean-Francois Bonfanti ,  Koenraad Jozef Lodewijk Andries ,  Jérôme Michel Claude Fortin ,  Philippe Muller ,  Frédéric Marc Maurice Doublet ,  Christophe Meyer ,  Rudy Edmond Willebrords ,  Tom Valerius Josepha Gevers ,  Philip Maria Martha Bern Timmerman

IPC分类号： A01N43/52 ,  A61K31/415 ,  C07D233/00 ,  C07D235/02 ,  C07D487/04 ,  C07D487/06 ,  C07D413/12

CPC分类号： C07D413/12 ,  C07D401/06 ,  C07D401/14 ,  C07D413/14

摘要： The present invention concerns morpholinyl containing benzimidazoles having inhibitory activity on the replication of the respiratory syncytial virus and having the formula a prodrug, N-oxide, addition salt, quaternary amine, metal complex or stereochemically isomeric form thereof. It further concerns the preparation thereof and compositions comprising these compounds, as well as the use thereof as a medicine.

摘要翻译： 本发明涉及对具有对呼吸道合胞病毒复制具有抑制活性的含有吗啉基的苯并咪唑，其具有前药，N-氧化物，加成盐，季胺，金属络合物或其立体化学异构形式。 还涉及其制备方法和包含这些化合物的组合物，以及作为药物的用途。

公开(公告)号：US08044073B2

公开(公告)日：2011-10-25

申请号：US10596514

申请日：2004-12-20

申请人： Jean-François Bonfanti ,  Koenraad Jozef Lodewijk Andries ,  Jér{hacek over (o)}me Michel Claude Fortin ,  Philippe Muller ,  Frédéric Marc Maurice Doublet ,  Christophe Meyer ,  Rudy Edmond Willebrords ,  Tom Valerius Josepha Gevers ,  Philip Maria Martha Bern Timmerman

发明人： Jean-François Bonfanti ,  Koenraad Jozef Lodewijk Andries ,  Jér{hacek over (o)}me Michel Claude Fortin ,  Philippe Muller ,  Frédéric Marc Maurice Doublet ,  Christophe Meyer ,  Rudy Edmond Willebrords ,  Tom Valerius Josepha Gevers ,  Philip Maria Martha Bern Timmerman

IPC分类号： A61K31/4439 ,  C07D401/04 ,  C07D401/06

CPC分类号： C07D401/06 ,  C07D235/20 ,  C07D235/30 ,  C07D401/12 ,  C07D401/14 ,  C07D403/02 ,  C07D405/14 ,  C07D471/04 ,  C07F9/65583

摘要： Aminobenzimidazoles and benzimidazoles having inhibitory activity on RSV replication and having the formula the prodrugs, N-oxides, addition salts, quaternary amines, metal complexes and stereochemically isomeric forms thereof; wherein G is a direct bond or C1-10alkanediyl optionally substituted with one or more hydroxy, C1-6alkyloxy, Ar1C1-6alkyloxy, C1-6alkylthio, Ar1C1-6alkylthio, HO(—CH2—CH2—O)n—, C1-6alkyloxy(—CH2—CH2—O)n— or Ar1C1-6alkyloxy(—CH2—CH2—O)n—; R1 is Ar1 or a monocyclic or bicyclic heterocycle; Q is hydrogen, amino or mono- or di(C1-4alkyl)amino; one of R2a and R3a is selected from halo, optionally mono- or polysubstituted C1-6alkyl, optionally mono- or polysubstituted C2-6alkenyl, nitro, hydroxy, Ar2, N(R4aR4b), N(R4aR4b)sulfonyl, N(R4aR4b)carbonyl, C1-6alkyloxy, Ar2oxy, Ar2C1-6alkyloxy, carboxyl, C1-6alkyloxycarbonyl, or —C(═Z)Ar2; and the other one of R2a and R3a is hydrogen; in case R2a is different from hydrogen then R2b is hydrogen, C1-6alkyl or halogen and R3b is hydrogen; in case R3a is different from hydrogen then R3b is hydrogen, C1-6alkyl or halogen and R2b is hydrogen. Compositions containing these compounds as active ingredient and processes for preparing these compounds and compositions.

摘要翻译： 对RSV复制具有抑制活性的氨基苯并咪唑和苯并咪唑，具有前药，N-氧化物，加成盐，季胺，金属络合物及其立体化学异构形式; 其中G是直接键或任选被一个或多个羟基，C 1-6烷氧基，Ar 1 C 1-6烷氧基，C 1-6烷硫基，Ar 1 C 1-6烷硫基，HO（-CH 2 -CH 2 -O）n - ，C 1-6烷氧基（ -CH 2 -CH 2 -O）n - 或Ar 1 C 1-6烷氧基（-CH 2 -CH 2 -O）n - R1是Ar1或单环或双环杂环; Q是氢，氨基或单或二（C 1-4烷基）氨基; R 2a和R 3a中的一个选自卤素，任选的单取代或多取代的C 1-6烷基，任选单取代或多取代的C 2-6烯基，硝基，羟基，Ar 2，N（R 4aR 4 b），N（R 4 R 4 b）磺酰基，N（R 4 R 4 b） ，C 1-6烷氧基，Ar 2氧基，Ar 2 C 1-6烷氧基，羧基，C 1-6烷氧基羰基或-C（= Z）Ar 2; R2a和R3a中的另一个是氢; 在R2a不同于氢的情况下，R2b为氢，C1-6烷基或卤素，R3b为氢; 在R3a不同于氢的情况下，R 3b是氢，C 1-6烷基或卤素，R 2b是氢。 含有这些化合物作为活性成分的组合物和制备这些化合物和组合物的方法。

公开(公告)号：US06420387B1

公开(公告)日：2002-07-16

申请号：US09689211

申请日：2000-10-12

申请人： Marc Gaston Venet ,  Patrick René Angibaud ,  Philippe Muller ,  Gérard Charles Sanz

发明人： Marc Gaston Venet ,  Patrick René Angibaud ,  Philippe Muller ,  Gérard Charles Sanz

IPC分类号： A61K31445

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D407/14 ,  C07D413/14 ,  Y02P20/55

摘要： This invention comprises the novel compounds of formula (I) wherein the dotted line represents an optional bond; X is oxygen or sulfur; R1 is hydrogen, C1-12alkyl, Ar1, Ar2C1-6alkyl, quinolinylC1-6alkyl, pyridylC1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, aminoC1-6alkyl, or a radical of formula —Alk1—C(═O)—R9, —Alk1—S(O)—R9 or —Alk1—S(O)2—R9; R2, R3 and R16 each independently are hydrogen, hydroxy, halo, cyano, C1-6alkyl, C1-6alkyloxy, hydroxyC1-6akyloxy, C1-6alkyloxyC1-6alkyloxy, aminoC1-6alkyloxy, mono- or di(C1-6alkyl)aminoC1-6alkyloxy, Ar1, Ar2C1-6alkyl, Ar2oxy, Ar2C1-6alkyloxy, hydroxycarbonyl, C1-6alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C2-6alkenyl; R4 and R5 each independently are hydrogen, halo, Ar1, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkyloxy, C1-6alkylthio, amino, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkylS(O)C1-6alkyl or C1-6alkylS(O)2C1-6alkyl; R6 and R7 each independently are hydrogen, halo, cyano, C1-6alkyl, 4,4-dimethyl-oxazolyl, C1-6alkyloxy or Ar2oxy; R8 is hydrogen, C1-6alkyl, cyano, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonylC1-6alkyl; cyanoC1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, carboxyC1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, imidazolyl, haloC1-6alkyl, C1-6alkyloxyC1-6alkyl, aminocarbonylC1-6alkyl, or a radical of formula —O—R10, —SR10, —N—R11R12; R17 is hydrogen, halo, cyano, C1-6alkyl, C1-6alkyloxycarbonyl, Ar1; R18 is hydrogen, C1-6alkyl, C1-6alkyloxy or halo; R19 is hydrogen or C1-6alkyl; having farnesyl transferase inhibiting activity; their preparation, compositions containing them and their use as a medicine.

摘要翻译： 本发明包括式（I）的新化合物，其中虚线表示任选的键; X是氧或硫; R1是氢，C1-12烷基，Ar1，Ar2C1-6烷基，喹啉基C 1-6烷基，吡啶基C 1-6烷基，羟基C 1-6烷基，C 1-6烷氧基C 1-6烷基，一或二（C 1-6烷基）氨基C 1-6烷基，氨基C 1-6烷基或 式-Alk1-C（= O）-R9，-Alk1-S（O）-R9或-Alk1-S（O）2-R9的基团; R 2，R 3和R 16各自独立地是氢，羟基，卤素，氰基，C 1-6烷基，C 1-6烷氧基，羟基C 1-6烷氧基，C 1-6烷氧基C 1-6烷氧基，氨基C 1-6烷氧基，一或二（C 1-6烷基）氨基C 1-6烷氧基 Ar 1，Ar 2 C 1-6烷基，Ar 2氧基，Ar 2 C 1-6烷氧基，羟基羰基，C 1-6烷氧基羰基，三卤代甲基，三卤代甲氧基，C 2-6烯基; R 4和R 5各自独立地是氢，卤素，Ar 1，C 1-6烷基，羟基C 1-6烷基，C 1-6烷氧基C 1-6烷基，C 1-6烷氧基，C 1-6烷硫基，氨基，羟基羰基，C 1-6烷氧基羰基，C 1-6烷基S（O） C 1-6烷基或C 1-6烷基S（O）2 C 1-6烷基; R 6和R 7各自独立地为氢，卤素，氰基，C 1-6烷基，4,4-二甲基 - 恶唑基，C 1-6烷氧基或Ar 2氧基; R 8是氢，C 1-6烷基，氰基，羟基羰基，C 1-6烷氧基羰基，C 1-6烷基羰基C 1-6