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：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：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：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：US20090062278A1

公开(公告)日：2009-03-05

申请号：US12253450

申请日：2008-10-17

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

IPC分类号： A61K31/5377 ,  A61K31/4545 ,  C07D211/06 ,  C07D413/14 ,  A61P31/12 ,  A61K31/496 ,  C07D403/14

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)naminocarbonyl, 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， Het 1硫基C 1-6烷基，Ar 3磺酰基C 1-6烷基，Het 1磺酰基C 1-6烷基，Ar 3氨基羰基，Het 1氨基羰基，Ar 3（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：US20080280881A1

公开(公告)日：2008-11-13

申请号：US12140686

申请日：2008-06-17

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

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

IPC分类号： A61K31/553 ,  C07D413/14 ,  A61K31/5377 ,  A61P31/12 ,  C07D267/02

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.