公开(公告)号：EP0966473B1

公开(公告)日：2002-07-24

申请号：EP98912552.1

申请日：1998-02-26

申请人： Aventis Pharma S.A.

发明人： HARDY, Jean-Claude ,  BOUQUEREL, Jean ,  NEMECEK, Patrick ,  ALOUP, Jean-Claude ,  MIGNANI, Serge ,  PEYRONEL, Jean-François

IPC分类号： C07D513/06 ,  A61K31/54 ,  A61K31/535 ,  A61K31/425 ,  C07D215/14 ,  C07D215/16 ,  C07D279/16 ,  C07D265/36 ,  C07D517/06

CPC分类号： C07D513/06

摘要： The invention concerns compounds of formula (I) in which R1 represents a sulphur or selenium atom, R2 represents hydrogen or alkyl, -R3-R4-R5- represents a chain of formula -CH2-CH2-CH2-, -CH(R7)-CH2-CH2-, -CH2-CH2-CH(R8)-, -CH2-CH(R9)-CH2-, -CH2-CH2-S-, -CH2-CH2-SO-, -CH2-CH2-SO2-, -CH2-CH2-Se-, -CH2-CH2-O-, -CH2-CH2-CO-, -CH2-CH2-N(R10)-, -CH2-CO-N(R10)-, -CH2-CF2-CH2-, -CH2-CF2-CH(OH)-, -CH2-CH(R13)-S-, -CH2-CH(R13)-SO-, or -CH2-CH(R13)-SO2-, R6 represents a polyfluoroalkyl, polyfluoroalcoxy or polyfluoroalkylthio radical, R7 represents alkyl, -CH2OH, -CH2-SO2-alk or -CH2-NR11R12, R8 represents alkyl, hydroxy, -CH2OH, -NR11R12, -CH2-NR11R12, -S-alk, -SO-alk, -SO2-alk, thienyl, furyl, phenyl, or phenyl substituted, R9 represents alkyl or -CH2OH, R10 represents hydrogen or alkyl, R11 represents hydrogen or alkyl, -CO-alk or -CO-CF3, R12 represents hydrogen or alkyl, or R11 and R12 form with the nitrogen atom to which they are bound a heterocyclic compound, R13 represents alkyl or -CH2OH, their salts, their methods of preparation, medicines containing them and the intermediates.

公开(公告)号：EP0820455B1

公开(公告)日：2001-10-31

申请号：EP96911018.8

申请日：1996-04-02

申请人： Aventis Pharma S.A.

发明人： ALOUP, Jean-Claude ,  AUDIAU, François ,  BARREAU, Michel ,  DAMOUR, Dominique ,  GENEVOIS-BORELLA, Arielle ,  HARDY, Jean-Claude ,  JIMONET, Patrick ,  MANFRE, Franco ,  MIGNANI, Serge ,  NEMECEK, Patrick ,  RIBEILL, Yves

IPC分类号： C07D487/04 ,  A61K31/495 ,  C07D233/90 ,  C07F9/6561 ,  C07F9/6506 ,  A61K31/675

CPC分类号： C07D487/04 ,  C07D233/90 ,  C07F9/65066 ,  C07F9/6561

摘要： Compounds of formula (I), wherein R is a hydrogen atom or a carboxy, alkoxycarbonyl, -CO-NR4R5, -PO3H2 or -CH2OH radical, and R1 is an -alk-NH2, -alk-NH-CO-R3, -alk-COOR4, -alk-CO-NR5R6 or -CO-NH-R7 radical. The compounds of formula (I) have valuable pharmacological properties and are antagonists of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor also known as the quisqualate receptor. Furthermore, the compounds of formula (I) are non-competitive antagonists of the N-methyl-D-aspartate (NMDA) receptor and more specifically are ligands for NMDA receptor glycine modulator sites.

公开(公告)号：EP1054882A1

公开(公告)日：2000-11-29

申请号：EP99903732.8

申请日：1999-02-11

申请人： Aventis Pharma S.A.

发明人： BAUDOIN, Bernard ,  CLERC, François ,  DEREU, Norbert ,  EL-AHMAD, Youssef ,  HARDY, Jean-Claude ,  JIMONET, Patrick ,  LE BRUN, Alain

IPC分类号： C07D311/68 ,  C07D405/12 ,  C07D335/06 ,  C07D409/12 ,  A61K31/35

CPC分类号： C07D335/06 ,  C07D311/68 ,  C07D405/12 ,  C07D409/12

摘要： The invention concerns novel products of general formula (I), their preparation, pharmaceutical compositions containing them and the use thereof for preparing medicines. In general formula (I) R1 represents a -CO-CH(NH2)-CH2SH, or -CH2-CH(NH2)-CH2SH, or -CHRi1Ri2 radical; R2 represents a hydrogen atom, an alkyl, aralkyl, aryl, alkylcarbonyl, aralkylcarbonyl, heterocycloalkyl radical; R3 represents a hydrogen atom or a halogen atom or an alkyl, aryl, aralkyl radical; R4 represents a -CHRi3Ri4 radical; R5 represents a hydrogen atom, or a -C(O)-Ri5 radical; R6 represents a hydrogen atom or an alkyl, aryl, aralkyl radical; R7, R8 represent a hydrogen atom or an alkyl, aryl, aralkyl radical; X represents a hydrogen atom or a -S(O)1 radical.

公开(公告)号：EP1000067A1

公开(公告)日：2000-05-17

申请号：EP98940327.4

申请日：1998-07-24

申请人： Aventis Pharma S.A.

发明人： HARDY, Jean-Claude ,  BOUQUEREL, Jean ,  NEMECEK, Patrick ,  PEYRONEL, Jean-François

IPC分类号： C07D513/06 ,  A61K31/55 ,  C07D517/06 ,  C07D223/16 ,  C07D281/02 ,  C07D243/14

CPC分类号： C07D513/06

摘要： The invention concerns compounds of formula (I) in which: R1 represents a sulphur or selenium atom; R2 represents a hydrogen atom or an alkyl radical; -R3-R4-R5-R6- represents a chain of formula -CH2-CH2-CH2-CH2-, -CH2-CH2-CH2-CO-, -CH2-CH2CH2CH(R8)-, -CH2-CH2-CH2-Se-, -CH2-CH2-Se-CH2-, -CH2-CH2-CH2-S-, -CH2-CH2-CH2-SO-, -CH2-CH2-CH2-SO2-, -CH2-CH2-CH2-O-, -CH2-CH2-CH2-N(R9)-, -CH2-CH2-CO-CH2-, -CH2-CH2CH(R8)-CH2-, -CH2-CH2-S-CH2-, -CH2-CH2-SO-CH2-, -CH2-CH2-SO2-CH2-, -CH2-C(alk)(alk')-S-CH2, -CH2-C(alk)(alk')-SO-CH2, -CH2-C(alk)(alk')-SO2-CH2, -CH2-CH(R10)-S-CH2-, -CH2-CH(R10)-SO-CH2-, -CH2-CH(R10)-SO2-CH2-, -CH2-CH2-O-CH2-, -CH2-CH2-N(R9)-CH2- or -CH2-CO-N(R9)-CH2-; R7 represents a polyalkyl or polyfluoroalkoxy radical; R8 represents a hydroxy radical; R9 represents a hydrogen atom or an alkyl or benzyl radical and R10 represents an alkyl radical, -CH2OH, -COOalk, -COOH or -CONH2, their isomers, racemic compounds, enantiomers, their salts, their methods of preparation and medicines containing them. Said compounds are anticonvulsant and interfere with glutamatergic transmission.

摘要翻译： 本发明涉及式（I）的化合物，其中：R 1表示硫或硒原子; R2代表氢原子或烷基; -R 3 -R 4 -R 5 -R 6 - 表示式-CH 2 -CH 2 -CH 2 -CH 2 - ，-CH 2 -CH 2 -CH 2 -CO - ， - CH 2 -CH 2 CH 2 CH（R 8） - ，-CH 2 -CH 2 -CH 2 - ，-CH 2 -CH 2 -CH 2 -CH 2 - ， - CH 2 -CH 2 -CH 2 -CH 2 - ， - CH 2 -CH 2 -CH 2 -SO 2 - ， - ，-CH 2 -CH 2 -CH 2 -N（R 9） - ， - CH 2 -CH 2 -CO-CH 2 - ， - CH 2 -CH 2 CH（R 8） （alk'） - S-CH 2，-CH 2 -C（烷基）（烷基）-SO-CH 2 - ， - CH 2 CH 2 -SO 2 -CH 2 - （烷基）（烷基）-SO 2 -CH 2，-CH 2 -CH（R 10）-S -CH 2 - ， - CH 2 -CH（R 10）-SO-CH 2 - ，-CH 2 -CH（R 10） -CH 2 - ， - CH 2 -CH 2 -O-CH 2 - ， - CH 2 -CH 2 -N（R 9）-CH 2 - 或-CH 2 -CO-N（R 9）-CH 2 - R7表示聚烷基或多氟烷氧基; R8代表羟基; R9代表氢原子或烷基或苄基，R10代表烷基，-CH2OH，-COOalk，-COOH或-CONH2，它们的异构体，外消旋化合物，对映异构体，它们的盐，它们的制备方法和含有它们的药物。 所述化合物是抗惊厥药并干扰谷氨酸能传递。

公开(公告)号：EP1000067B1

公开(公告)日：2002-10-23

申请号：EP98940327.4

申请日：1998-07-24

申请人： Aventis Pharma S.A.

发明人： HARDY, Jean-Claude ,  BOUQUEREL, Jean ,  NEMECEK, Patrick ,  PEYRONEL, Jean-François

IPC分类号： C07D513/06 ,  A61K31/55 ,  C07D517/06 ,  C07D223/16 ,  C07D281/02 ,  C07D243/14

CPC分类号： C07D513/06

摘要： The invention concerns compounds of formula (I) in which: R1 represents a sulphur or selenium atom; R2 represents a hydrogen atom or an alkyl radical; -R3-R4-R5-R6- represents a chain of formula -CH2-CH2-CH2-CH2-, -CH2-CH2-CH2-CO-, -CH2-CH2CH2CH(R8)-, -CH2-CH2-CH2-Se-, -CH2-CH2-Se-CH2-, -CH2-CH2-CH2-S-, -CH2-CH2-CH2-SO-, -CH2-CH2-CH2-SO2-, -CH2-CH2-CH2-O-, -CH2-CH2-CH2-N(R9)-, -CH2-CH2-CO-CH2-, -CH2-CH2CH(R8)-CH2-, -CH2-CH2-S-CH2-, -CH2-CH2-SO-CH2-, -CH2-CH2-SO2-CH2-, -CH2-C(alk)(alk')-S-CH2, -CH2-C(alk)(alk')-SO-CH2, -CH2-C(alk)(alk')-SO2-CH2, -CH2-CH(R10)-S-CH2-, -CH2-CH(R10)-SO-CH2-, -CH2-CH(R10)-SO2-CH2-, -CH2-CH2-O-CH2-, -CH2-CH2-N(R9)-CH2- or -CH2-CO-N(R9)-CH2-; R7 represents a polyalkyl or polyfluoroalkoxy radical; R8 represents a hydroxy radical; R9 represents a hydrogen atom or an alkyl or benzyl radical and R10 represents an alkyl radical, -CH2OH, -COOalk, -COOH or -CONH2, their isomers, racemic compounds, enantiomers, their salts, their methods of preparation and medicines containing them. Said compounds are anticonvulsant and interfere with glutamatergic transmission.

公开(公告)号：EP0880522B1

公开(公告)日：2001-09-19

申请号：EP97900236.7

申请日：1997-01-06

申请人： Aventis Pharma S.A.

发明人： ALOUP, Jean-Claude ,  BOUQUEREL, Jean ,  DAMOUR, Dominique ,  HARDY, Jean-Claude ,  JIMONET, Patrick ,  MANFRE, Franco ,  MIGNANI, Serge ,  NEMECEK, Patrick

IPC分类号： C07D487/04 ,  C07D233/90 ,  A61K31/495 ,  C07F9/6561 ,  C07F9/6506

CPC分类号： C07D487/04 ,  C07F9/6561

摘要： Compounds of formula (I), wherein R is a hydrogen atom or a -COOH, -alk-COOH, -PO3H2, -CH2-PO3H2, or -CH=CH-COOH radical, or a phenyl radical substituted by a carboxy radical, R1 is an alk-CN, -alk-COOH, -alk-Het, alk-PO3H2 or -alk-CO-NH-SO2R2 radical, R2 is an alkyl or phenyl radical, alk is an alkyl radical, Het is a saturated or unsaturated mono- or polycyclic heterocyclic ring containing 1-9 carbon atoms and one or more heteroatoms selected from O, S and N, said heterocyclic ring optionally being substituted by one or more alkyl, phenyl or phenylalkyl radicals, with the proviso that when R is a hydrogen atom or a -COOH or -PO3H2 radical, R1 cannot be -alk-COOH, isomers, racemic mixtures, enantiomers and diastereoisomers thereof, salts thereof, the preparation thereof, intermediates thereof and drugs containing said compounds, are disclosed. The compounds of formula (I) have valuable pharmacological properties and are antagonists of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor also known as the quisqualate receptor. Furthermore, the compounds of formula (I) are non-competitive antagonists of the N-methyl-D-aspartate (NMDA) receptor, and specifically ligands for NMDA receptor glycine modulator sites.