公开(公告)号：PE20081703A1

公开(公告)日：2009-01-14

申请号：PE2008000167

申请日：2008-01-23

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  LE DIGUARHER THIERRY ,  GENESTE OLIVER ,  HICKMAN JOHN

IPC: A61K31/4985 ,  A61P35/00 ,  C07D471/00 ,  C07D471/04

Abstract: REFERIDA A UN COMPUESTO TRICICLICO DE FORMULA (I), DONDE A ES UN CICLO AROMATICO O NO AROMATICO QUE CONTIENE 5, 6 O 7 ESLABONES QUE PUEDE CONTENER 1 O 2 HETEROATOMOS TALES COMO O, S Y N. n Y n' SON 0, 1 O 2 DONDE LA SUMA DE n Y n' ESTA ENTRE 0 Y 4; R3 ES ARILO O HETEROARILO; X ES UN ALQUILENO C1-C6 OPCIONALMENTE SUSTITUIDO CON OXIGENO, CICLOALQUILENO, ARILENO, HETEROARILENO O SO2; R1 Y R2 SON H O UN COMPUESTO DE FORMULA (II); Y ES C=O O CH2; R5 ES H; R6 ES H O UN GRUPO -NR7R7' O -CH2-NR7R7'; R7 Y R7' SON H, ALQUILO C1-C6, ENTRE OTROS. SON COMPUESTOS PREFERIDOS: N-({(4aR)-3-[(4'-CLORO[1,1'-BIFENIL]-2-IL)METIL]-2,3,4,4a,5,6-HEXAHIDRO-1H-PIRAZINO[1,2-a]QUINOLIN-8-IL}CARBONIL)-4-({(1R)-3-(DIMETILAMINO)-1-[(FENILSULFANIL)-METIL]PROPIL}AMINO)-3-NITROBENCENOSULFONAMIDA, N-({(4aR)-3-[(4'-CLORO[1,1'-BIFENIL]-2-IL)METIL]-2,3,4,4a,5,6-HEXAHIDRO-1H-PIRAZINO[1,2-a]QUINOLIN-8-IL}CARBONIL)-4-({(1R)-3-((1R,5S)-3-AZABICICLO[3.1.0]HEX-3-IL)-1-[(FENILSULFANIL)-METIL]PROPIL}AMINO)-3-NITROBENCENOSULFONAMIDA, N-({(10aß)-2-[(4'-CLORO[1,1'-BIFENIL]-2-IL)METIL]-1,2,3,4,10,10a-HEXAHIDROPIRAZINO[1,2-a]INDOL-8-IL}CARBONIL)-4-({(1R)-3-(DIMETILAMINO)-1-[(FENILSULFANIL)METIL]PROPIL}AMINO)-3-NITROBENCENOSULFONAMIDA. TAMBIEN ESTA REFERIDA A UN PROCEDIMIENTO DE PREPARACION Y A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS TIENEN ACTIVIDAD PRO-APOPTOTICA Y SON UTILES EN EL TRATAMIENTO DEL CANCER

公开(公告)号：PE17032008A1

公开(公告)日：2009-01-14

申请号：PE0001672008

申请日：2008-01-23

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  LE DIGUARHER THIERRY ,  GENESTE OLIVER ,  HICKMAN JOHN

IPC: A61K31/4985 ,  A61P35/00 ,  C07D471/00 ,  C07D471/04

CPC classification number: C07D471/04 ,  C07D487/04

Abstract: REFERIDA A UN COMPUESTO TRICICLICO DE FORMULA (I), DONDE A ES UN CICLO AROMATICO O NO AROMATICO QUE CONTIENE 5, 6 O 7 ESLABONES QUE PUEDE CONTENER 1 O 2 HETEROATOMOS TALES COMO O, S Y N. n Y n' SON 0, 1 O 2 DONDE LA SUMA DE n Y n' ESTA ENTRE 0 Y 4; R3 ES ARILO O HETEROARILO; X ES UN ALQUILENO C1-C6 OPCIONALMENTE SUSTITUIDO CON OXIGENO, CICLOALQUILENO, ARILENO, HETEROARILENO O SO2; R1 Y R2 SON H O UN COMPUESTO DE FORMULA (II); Y ES C=O O CH2; R5 ES H; R6 ES H O UN GRUPO -NR7R7' O -CH2-NR7R7'; R7 Y R7' SON H, ALQUILO C1-C6, ENTRE OTROS. SON COMPUESTOS PREFERIDOS: N-({(4aR)-3-[(4'-CLORO[1,1'-BIFENIL]-2-IL)METIL]-2,3,4,4a,5,6-HEXAHIDRO-1H-PIRAZINO[1,2-a]QUINOLIN-8-IL}CARBONIL)-4-({(1R)-3-(DIMETILAMINO)-1-[(FENILSULFANIL)-METIL]PROPIL}AMINO)-3-NITROBENCENOSULFONAMIDA, N-({(4aR)-3-[(4'-CLORO[1,1'-BIFENIL]-2-IL)METIL]-2,3,4,4a,5,6-HEXAHIDRO-1H-PIRAZINO[1,2-a]QUINOLIN-8-IL}CARBONIL)-4-({(1R)-3-((1R,5S)-3-AZABICICLO[3.1.0]HEX-3-IL)-1-[(FENILSULFANIL)-METIL]PROPIL}AMINO)-3-NITROBENCENOSULFONAMIDA, N-({(10aß)-2-[(4'-CLORO[1,1'-BIFENIL]-2-IL)METIL]-1,2,3,4,10,10a-HEXAHIDROPIRAZINO[1,2-a]INDOL-8-IL}CARBONIL)-4-({(1R)-3-(DIMETILAMINO)-1-[(FENILSULFANIL)METIL]PROPIL}AMINO)-3-NITROBENCENOSULFONAMIDA. TAMBIEN ESTA REFERIDA A UN PROCEDIMIENTO DE PREPARACION Y A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS TIENEN ACTIVIDAD PRO-APOPTOTICA Y SON UTILES EN EL TRATAMIENTO DEL CANCER

公开(公告)号：PL1720544T3

公开(公告)日：2008-05-30

申请号：PL05717646

申请日：2005-02-18

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  CHOLLET ANNE-MARIE ,  DHAINAUT ALAIN ,  BERT LIONEL ,  LESTAGE PIERRE ,  LOCKHART BRIAN

IPC: A61P25/00 ,  A61K31/403 ,  C07D209/52 ,  C07D403/12

公开(公告)号：ZA200606558B

公开(公告)日：2008-01-08

申请号：ZA200606558

申请日：2006-08-07

Applicant: SERVIER LAB

Inventor： BERT LIONEL ,  CHOLLET ANNE MARIE ,  CASARA PATRICK ,  LESTAGE PIERRE ,  LOCKHART BRIAN ,  DHAINAUT ALAIN

IPC: C07D209/52 ,  C07D403/12

Abstract: Azabicyclic derivatives (I) are new. Azabicyclic derivatives of formula (I) and their enantiomers, diastereoisomers or acid or base addition salts are new. ALK : alkylene, 2-6C alkenylene (contains 1-3 double bonds) or 2-6C alkynylene (contains 1-3 triple bonds); Y, Y 1> : H, halo, alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, SH, OH, perhaloalkyl, nitro, amino (optionally substituted by one or two alkyl), acyl of formula C(O)R1a, aminocarbonyl (optionally N-substituted by one or two alkyl), acylamino (optionally N-substituted by alkyl), alkoxycarbonyl, COOH, sulfo or CN; R1a : H or alkyl; X : O, S or NR; R : H or alkyl; W 1> : CN (only when X = O or NR), N(R 1>)Z 1>R 2>or Z 1>NR 1>R 2>; Z 1> : C(O), C(S), C(NR 4>), C(O)N(R 3>), C(S)N(R 3>), C(NR 4>)N(R 3>), C(O)O, C(S)O or S(O) r; r : 1 or 2; Z 2> : C(O), C(S), C(NR 4>), S(O) ror bond; R 1>-R 4> : alkyl, 3-6C alkenyl (contains 1-3 double bonds), 3-6C alkynyl (contains 1-3 triple bonds), cycloalkyl, heterocycloalkyl, aryl or heteroaryl (all optionally substituted), alkoxy or H; or R 1>+R 2>or R 2>+R 3> : heterocyclyl or heteroaryl (both optionally substituted); m, n : 0-2, where the sum of m+n is 2 or 3; and p, q : 0-2. alkyl = 1-6C unless specified; perhaloalkyl = 1-3C with 1-7 halogen; aryl = phenyl, naphthyl, indanyl, indenyl, dihydronaphthyl or tetrahydronaphthyl; cycloalkyl = 3-11 membered mono- or bi-cyclic ring system, optionally with 1 or 2 unsaturations; heterocyclyl = 4-11 membered mono- or bicyclic ring system optionally with 1 or 2 unsaturations and/or 1-4 heteroatoms from N, O and/or S; heteroaryl = 5-11 membered mono- or bicyclic ring system with 1-4 heteroatoms from N, O and/or S; for cycloalkyl, aryl, heteroaryl or heterocyclyl, 'optionally substituted' comprises 1-3 substituents from alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, halogen, OH, SH, perhaloalkyl, nitro, amino or aminocarbonyl (optionally substituted by 1 or 2 alkyl), C(O)R1a, NHC(O)R1a (optionally N-substituted by alkyl), alkoxycarbonyl, COOH, sulfo or CN; or aryl, heteroaryl, cycloalkyl, heterocyclyl or benzyl with one or two optional oxo substituents where possible; for alkyl, alkenyl or alkynyl, 'optionally substituted ' comprises one or two of alkylthio, alkylsulfinyl, alkylsulfonyl, alkoxy, halogen, OH, SH, nitro, amino, C(O)R1a, aminocarbonyl, NHC(O)R1a, alkoxycarbonyl, COOH, sulfo, CN or aryl, heteroaryl, cycloalkyl, heterocylyl or aryloxy (all optionally substituted). An independent claim is included for the preparation of (I). [Image] ACTIVITY : Nootropic; Neuroprotective; Anticonvulsant; Tranquilizer; Anorectic; Analgesic. MECHANISM OF ACTION : Histamine (H3) activator. The ability of (I) to activate histamine was tested in mice. The results showed that 4-(3-hexahydrocyclopenta[c]-pyrrol-2(1H)-ylpropoxy)benzonitrile oxalate exhibited the percentage increase of N-methylhistamine in brain of 92%.

公开(公告)号：FR2866647B1

公开(公告)日：2006-10-27

申请号：FR0401690

申请日：2004-02-20

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  CHOLLET ANNE MARIE ,  DHAINAUT ALAIN ,  BERT LIONEL ,  LESTAGE PIERRE ,  LOCKHART BRIAN

IPC: C07D209/52 ,  A61K31/403 ,  A61P25/00 ,  C07D403/12

Abstract: Azabicyclic derivatives (I) are new. Azabicyclic derivatives of formula (I) and their enantiomers, diastereoisomers or acid or base addition salts are new. ALK : alkylene, 2-6C alkenylene (contains 1-3 double bonds) or 2-6C alkynylene (contains 1-3 triple bonds); Y, Y 1> : H, halo, alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, SH, OH, perhaloalkyl, nitro, amino (optionally substituted by one or two alkyl), acyl of formula C(O)R1a, aminocarbonyl (optionally N-substituted by one or two alkyl), acylamino (optionally N-substituted by alkyl), alkoxycarbonyl, COOH, sulfo or CN; R1a : H or alkyl; X : O, S or NR; R : H or alkyl; W 1> : CN (only when X = O or NR), N(R 1>)Z 1>R 2>or Z 1>NR 1>R 2>; Z 1> : C(O), C(S), C(NR 4>), C(O)N(R 3>), C(S)N(R 3>), C(NR 4>)N(R 3>), C(O)O, C(S)O or S(O) r; r : 1 or 2; Z 2> : C(O), C(S), C(NR 4>), S(O) ror bond; R 1>-R 4> : alkyl, 3-6C alkenyl (contains 1-3 double bonds), 3-6C alkynyl (contains 1-3 triple bonds), cycloalkyl, heterocycloalkyl, aryl or heteroaryl (all optionally substituted), alkoxy or H; or R 1>+R 2>or R 2>+R 3> : heterocyclyl or heteroaryl (both optionally substituted); m, n : 0-2, where the sum of m+n is 2 or 3; and p, q : 0-2. alkyl = 1-6C unless specified; perhaloalkyl = 1-3C with 1-7 halogen; aryl = phenyl, naphthyl, indanyl, indenyl, dihydronaphthyl or tetrahydronaphthyl; cycloalkyl = 3-11 membered mono- or bi-cyclic ring system, optionally with 1 or 2 unsaturations; heterocyclyl = 4-11 membered mono- or bicyclic ring system optionally with 1 or 2 unsaturations and/or 1-4 heteroatoms from N, O and/or S; heteroaryl = 5-11 membered mono- or bicyclic ring system with 1-4 heteroatoms from N, O and/or S; for cycloalkyl, aryl, heteroaryl or heterocyclyl, 'optionally substituted' comprises 1-3 substituents from alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, halogen, OH, SH, perhaloalkyl, nitro, amino or aminocarbonyl (optionally substituted by 1 or 2 alkyl), C(O)R1a, NHC(O)R1a (optionally N-substituted by alkyl), alkoxycarbonyl, COOH, sulfo or CN; or aryl, heteroaryl, cycloalkyl, heterocyclyl or benzyl with one or two optional oxo substituents where possible; for alkyl, alkenyl or alkynyl, 'optionally substituted ' comprises one or two of alkylthio, alkylsulfinyl, alkylsulfonyl, alkoxy, halogen, OH, SH, nitro, amino, C(O)R1a, aminocarbonyl, NHC(O)R1a, alkoxycarbonyl, COOH, sulfo, CN or aryl, heteroaryl, cycloalkyl, heterocylyl or aryloxy (all optionally substituted). An independent claim is included for the preparation of (I). [Image] ACTIVITY : Nootropic; Neuroprotective; Anticonvulsant; Tranquilizer; Anorectic; Analgesic. MECHANISM OF ACTION : Histamine (H3) activator. The ability of (I) to activate histamine was tested in mice. The results showed that 4-(3-hexahydrocyclopenta[c]-pyrrol-2(1H)-ylpropoxy)benzonitrile oxalate exhibited the percentage increase of N-methylhistamine in brain of 92%.

公开(公告)号：NO20064160A

公开(公告)日：2006-09-14

申请号：NO20064160

申请日：2006-09-14

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  LOCKHART BRIAN ,  LESTAGE PIERRE ,  DHAINAUT ALAIN ,  CHOLLET ANNE-MARIE ,  BERT LIONEL

IPC: C07D209/52 ,  C07D403/12

CPC classification number: C07D209/52 ,  C07D403/12

Abstract: Azabicyclic derivatives (I) are new. Azabicyclic derivatives of formula (I) and their enantiomers, diastereoisomers or acid or base addition salts are new. ALK : alkylene, 2-6C alkenylene (contains 1-3 double bonds) or 2-6C alkynylene (contains 1-3 triple bonds); Y, Y 1> : H, halo, alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, SH, OH, perhaloalkyl, nitro, amino (optionally substituted by one or two alkyl), acyl of formula C(O)R1a, aminocarbonyl (optionally N-substituted by one or two alkyl), acylamino (optionally N-substituted by alkyl), alkoxycarbonyl, COOH, sulfo or CN; R1a : H or alkyl; X : O, S or NR; R : H or alkyl; W 1> : CN (only when X = O or NR), N(R 1>)Z 1>R 2>or Z 1>NR 1>R 2>; Z 1> : C(O), C(S), C(NR 4>), C(O)N(R 3>), C(S)N(R 3>), C(NR 4>)N(R 3>), C(O)O, C(S)O or S(O) r; r : 1 or 2; Z 2> : C(O), C(S), C(NR 4>), S(O) ror bond; R 1>-R 4> : alkyl, 3-6C alkenyl (contains 1-3 double bonds), 3-6C alkynyl (contains 1-3 triple bonds), cycloalkyl, heterocycloalkyl, aryl or heteroaryl (all optionally substituted), alkoxy or H; or R 1>+R 2>or R 2>+R 3> : heterocyclyl or heteroaryl (both optionally substituted); m, n : 0-2, where the sum of m+n is 2 or 3; and p, q : 0-2. alkyl = 1-6C unless specified; perhaloalkyl = 1-3C with 1-7 halogen; aryl = phenyl, naphthyl, indanyl, indenyl, dihydronaphthyl or tetrahydronaphthyl; cycloalkyl = 3-11 membered mono- or bi-cyclic ring system, optionally with 1 or 2 unsaturations; heterocyclyl = 4-11 membered mono- or bicyclic ring system optionally with 1 or 2 unsaturations and/or 1-4 heteroatoms from N, O and/or S; heteroaryl = 5-11 membered mono- or bicyclic ring system with 1-4 heteroatoms from N, O and/or S; for cycloalkyl, aryl, heteroaryl or heterocyclyl, 'optionally substituted' comprises 1-3 substituents from alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, halogen, OH, SH, perhaloalkyl, nitro, amino or aminocarbonyl (optionally substituted by 1 or 2 alkyl), C(O)R1a, NHC(O)R1a (optionally N-substituted by alkyl), alkoxycarbonyl, COOH, sulfo or CN; or aryl, heteroaryl, cycloalkyl, heterocyclyl or benzyl with one or two optional oxo substituents where possible; for alkyl, alkenyl or alkynyl, 'optionally substituted ' comprises one or two of alkylthio, alkylsulfinyl, alkylsulfonyl, alkoxy, halogen, OH, SH, nitro, amino, C(O)R1a, aminocarbonyl, NHC(O)R1a, alkoxycarbonyl, COOH, sulfo, CN or aryl, heteroaryl, cycloalkyl, heterocylyl or aryloxy (all optionally substituted). An independent claim is included for the preparation of (I). [Image] ACTIVITY : Nootropic; Neuroprotective; Anticonvulsant; Tranquilizer; Anorectic; Analgesic. MECHANISM OF ACTION : Histamine (H3) activator. The ability of (I) to activate histamine was tested in mice. The results showed that 4-(3-hexahydrocyclopenta[c]-pyrrol-2(1H)-ylpropoxy)benzonitrile oxalate exhibited the percentage increase of N-methylhistamine in brain of 92%.

公开(公告)号：CA2367306C

公开(公告)日：2006-07-11

申请号：CA2367306

申请日：2002-01-17

Applicant: SERVIER LAB

Inventor： GUILBAUD NICOLAS ,  PIERRE ALAIN ,  LE DIGUARHER THIERRY ,  HICKMAN JOHN ,  DOREY GILBERT ,  CASARA PATRICK ,  TUCKER GORDON

IPC: C07C13/24 ,  C07C317/00 ,  A61K31/015 ,  A61K31/4164 ,  A61K31/417 ,  A61K31/4178 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/454 ,  A61P9/00 ,  A61P9/10 ,  A61P25/00 ,  A61P35/00 ,  C07D213/36 ,  C07D213/38 ,  C07D213/57 ,  C07D233/54 ,  C07D233/56 ,  C07D233/58 ,  C07D233/61 ,  C07D233/64 ,  C07D401/06

Abstract: L'invention concerne de nouveaux composés répondant à la formule formule (I ): dans laquelle X représente une liaison ou un groupement alkylène, CO, S(O)n, *- S(O)n-A1-, *-CO-A1-, -A1-S(O)n-A'1- et -A1-CO-A'1- dans lesquels A1 et A'1, identiques ou différents, représentent un groupement alkylène et n vaut 0, 1 ou 2, le symbole "*" représentant le point de rattachement du groupement au cycloheptène; Y représente un groupement aryle, hétéroaryle, cycloalkyle ou hétérocycloalkyle; R1, R2, R3 et R4 représentent indépendamment l'un de l'autre un atome d'hydrogène ou un groupement aryle, hétéroaryle, cycloalkyle ou hétérocycloalkyle, ou bien R1, R2, R3 et R4, pris deux à deux , forment ensemble une liaison, ou bien R1 et R2, ou R2 et R3 ou R3 et R4, pris deux à deux avec les atomes de carbone auxquels ils sont liés, forment un cycle benzénique fusion né ou un hétérocycle fusionné aromatique ou partiellement hydrogéné; T représente un groupement -CH(R5)-, -N(R5)- ou *-N(R5)CO- dans lesquels R5 représente un atome d'hydrogène ou un groupement alkyle, aryle, hétéroaryle, arylalkyle ou hétéroarylalkyle, le symbole "*" représentant le point de rattachement du groupement au cycloheptène; V représente un atome d'hydrogène ou un groupement aryle ou hétéroaryle; A2 représente un groupement [C(R6)(R'6)]p où p vaut 0, 1, 2, 3 ou 4 lorsque T représente un groupement - CH(R5)- ou *-N(R5)CO- où p vaut 1, 2, 3 ou 4 lorsque T représente un groupement -N(R5)- , et R6 et R'6, identiques ou différents, représentent un atome d'hydrogène ou un groupement alkyle, alkényle, alkynyle, aryle, hétéroaryle, hétérocycloalkyle, arylalkyle éventuellement substitué, hétéroarylalkyle, hétérocycloalkylalkyle, R9 ou alkyle substitué par un groupement R9 où R9 représente un groupement -OR5,-N(R5)(R'5), -S(O)m R5, -CON(R5)(R'5), -N(R5)COR'5, -N(R5)SO2R'5, -SO2N(R5)(R'5), -N(R5)COO(R'5), m étant égal à 0, 1 ou 2, et R'5 prenant toutes les valeurs de R5. L'invention vise également les énantiomères et diastéréoisomères des composés de formule (I), ainsi que leu rs sels -52- d'addition à un acide ou à une base pharmaceutiquement acceptable. Les composés selon l'invention sont utiles à titre de médicaments pour le traitement des maladi es cancéreuses ainsi que pour le traitement de la resténose après angioplastie ou chirurgie vasculaire, et de la neurofibromatose de type I.

公开(公告)号：FR2866647A1

公开(公告)日：2005-08-26

申请号：FR0401690

申请日：2004-02-20

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  CHOLLET ANNE MARIE ,  DHAINAUT ALAIN ,  BERT LIONEL ,  LESTAGE PIERRE ,  LOCKHART BRIAN

IPC: C07D209/52 ,  C07D403/12 ,  A61K31/403 ,  A61P25/00

Abstract: Azabicyclic derivatives (I) are new. Azabicyclic derivatives of formula (I) and their enantiomers, diastereoisomers or acid or base addition salts are new. ALK : alkylene, 2-6C alkenylene (contains 1-3 double bonds) or 2-6C alkynylene (contains 1-3 triple bonds); Y, Y 1> : H, halo, alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, SH, OH, perhaloalkyl, nitro, amino (optionally substituted by one or two alkyl), acyl of formula C(O)R1a, aminocarbonyl (optionally N-substituted by one or two alkyl), acylamino (optionally N-substituted by alkyl), alkoxycarbonyl, COOH, sulfo or CN; R1a : H or alkyl; X : O, S or NR; R : H or alkyl; W 1> : CN (only when X = O or NR), N(R 1>)Z 1>R 2>or Z 1>NR 1>R 2>; Z 1> : C(O), C(S), C(NR 4>), C(O)N(R 3>), C(S)N(R 3>), C(NR 4>)N(R 3>), C(O)O, C(S)O or S(O) r; r : 1 or 2; Z 2> : C(O), C(S), C(NR 4>), S(O) ror bond; R 1>-R 4> : alkyl, 3-6C alkenyl (contains 1-3 double bonds), 3-6C alkynyl (contains 1-3 triple bonds), cycloalkyl, heterocycloalkyl, aryl or heteroaryl (all optionally substituted), alkoxy or H; or R 1>+R 2>or R 2>+R 3> : heterocyclyl or heteroaryl (both optionally substituted); m, n : 0-2, where the sum of m+n is 2 or 3; and p, q : 0-2. alkyl = 1-6C unless specified; perhaloalkyl = 1-3C with 1-7 halogen; aryl = phenyl, naphthyl, indanyl, indenyl, dihydronaphthyl or tetrahydronaphthyl; cycloalkyl = 3-11 membered mono- or bi-cyclic ring system, optionally with 1 or 2 unsaturations; heterocyclyl = 4-11 membered mono- or bicyclic ring system optionally with 1 or 2 unsaturations and/or 1-4 heteroatoms from N, O and/or S; heteroaryl = 5-11 membered mono- or bicyclic ring system with 1-4 heteroatoms from N, O and/or S; for cycloalkyl, aryl, heteroaryl or heterocyclyl, 'optionally substituted' comprises 1-3 substituents from alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, halogen, OH, SH, perhaloalkyl, nitro, amino or aminocarbonyl (optionally substituted by 1 or 2 alkyl), C(O)R1a, NHC(O)R1a (optionally N-substituted by alkyl), alkoxycarbonyl, COOH, sulfo or CN; or aryl, heteroaryl, cycloalkyl, heterocyclyl or benzyl with one or two optional oxo substituents where possible; for alkyl, alkenyl or alkynyl, 'optionally substituted ' comprises one or two of alkylthio, alkylsulfinyl, alkylsulfonyl, alkoxy, halogen, OH, SH, nitro, amino, C(O)R1a, aminocarbonyl, NHC(O)R1a, alkoxycarbonyl, COOH, sulfo, CN or aryl, heteroaryl, cycloalkyl, heterocylyl or aryloxy (all optionally substituted). An independent claim is included for the preparation of (I). [Image] ACTIVITY : Nootropic; Neuroprotective; Anticonvulsant; Tranquilizer; Anorectic; Analgesic. MECHANISM OF ACTION : Histamine (H3) activator. The ability of (I) to activate histamine was tested in mice. The results showed that 4-(3-hexahydrocyclopenta[c]-pyrrol-2(1H)-ylpropoxy)benzonitrile oxalate exhibited the percentage increase of N-methylhistamine in brain of 92%.

公开(公告)号：DE60105001T2

公开(公告)日：2005-08-18

申请号：DE60105001

申请日：2001-03-06

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  PERRON-SIERRA FRANCOISE ,  ATASSI GHANEM ,  TUCKER GORDON ,  SAINT-DIZIER DOMINIQUE

IPC: C07D233/24 ,  A61K31/4164 ,  A61K31/4168 ,  A61K31/417 ,  A61K31/4184 ,  A61K31/426 ,  A61K31/4375 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/505 ,  A61K31/55 ,  A61P9/00 ,  A61P19/10 ,  A61P27/02 ,  A61P29/00 ,  A61P33/14 ,  A61P35/00 ,  A61P43/00 ,  C07D213/36 ,  C07D213/74 ,  C07D223/04 ,  C07D223/12 ,  C07D233/48 ,  C07D233/54 ,  C07D235/10 ,  C07D235/14 ,  C07D235/30 ,  C07D239/14 ,  C07D277/18 ,  C07D277/20 ,  C07D277/42 ,  C07D401/12 ,  C07D403/12 ,  C07D471/04

Abstract: Compounds of formula (1):wherein:G represents an optionally substituted phenyl or optionally substituted heterocycle, G1 and G2 being N or C,T1 represents -CH2-CH2-, -CH=CH- or =CH-CH2-, and T2 is a bond, or T1 represents -CH2- or =CH- and T2 is -CH2-, =CH-,R5 represents -(CH2)m-COOR6,R6 and R6' represent hydrogen, alkyl, optionally substituted aryl or optionally substituted arylalkyl,A represents -CO-, -CH2-, =CH- or -CH= and W represents -CH-, =C- or -C=, or A represents -CO- or -CH2- and W represents N,X represents -CO-X1-, -CO-NR6-X1-, -NR6-CO-X1-, -O-X1-, -SO2-NR6-X1- or -S(O)n-X1-,Y represents -Y1-, -Y2-Y1- or -Y1-Y2-Y1-, Y1 being an alkylene, alkenylene or alkynylene, and Y2 being an arylene, heteroarylene, cycloalkylene or heterocycloalkylene,Z represents -Z1-, -Z10-NR6-, and -Z10-NR6-CO-, Z1 being a heteroaryl, heterocycloalkyl, heteroarylalkyl, heterocycloalkylalkyl, fused arylheteroaryl, fused arylheterocycloalkyl, fused heteroarylheterocycloalkyl, fused heterocycloalkylheteroaryl or fused heteroarylheteroaryl, each of which is optionally substituted, or a group,Z2-NR6 or Z2-NR6-CO, Z2 being a group Z1, alkyl or heteroalkyl, andZ10 represents Z1 or an alkyl,its enantiomers, diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base,and medicinal products containing the same which are useful as vitronectin receptor antagonists.

公开(公告)号：EA004859B1

公开(公告)日：2004-08-26

申请号：EA200200048

申请日：2002-01-17

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  LE DIGUARHER THIERRY ,  DOREY GILBERT ,  HICKMAN JOHN ,  PIERRE ALAIN ,  TUCKER GORDON ,  GUILBAUD NICOLAS

IPC: C07C317/00 ,  A61K31/4164 ,  A61K31/417 ,  A61K31/4178 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/454 ,  A61P9/00 ,  A61P9/10 ,  A61P25/00 ,  A61P35/00 ,  C07D213/36 ,  C07D213/38 ,  C07D213/57 ,  C07D233/54 ,  C07D233/58 ,  C07D233/61 ,  C07D233/64 ,  C07D401/06 ,  C07D211/82 ,  A61K31/4174

Abstract: Соединенияформулы (I)где X представляетсобойсвязьилиалкиленовую, СО, S(O), -S(O)-A-, -СО-А, -А-S(O)-A'- или -A-CO-A'-группу, Y представляетсобойарильную, гетероарильную, циклоалкильнуюилигетероциклоалкильнуюгруппу, каждаяизкоторыхнезамещенаилизамещена, R, R, Rи R, каждаянезависимоотдругих, представляютсобойатомводородаилиарильную, гетероарильную, циклоалкильнуюилигетероциклоалкильнуюгруппу, каждаяизкоторыхнезамещенаилизамещена, или R, R, Rи R, взятыепопарно, вместеобразуютсвязьилиобразуютслитоебензольноекольцо, илислитыйароматический, иличастичноненасыщенныйгетероцикл, Тпредставляетсобойгруппу -CH(R)-, -N(R)- или -N(R)CO-, V представляетсобойатомводородаилинезамещеннуюилизамещеннуюарильнуюилигетероарильнуюгруппу, Апредставляетсобойгруппу [C(R)(R')], Rи Rимеютзначения, указанныев описании. Фармацевтическиекомпозиции.