公开(公告)号：AT302750T

公开(公告)日：2005-09-15

申请号：AT01955425

申请日：2001-07-16

Applicant: SERVIER LAB

Inventor： DESCAMPS-FRANCOIS CAROLE ,  YOUS SAID ,  LESIEUR DANIEL ,  GUILLAUMET GERALD ,  VIAUD MARIE-CLAUDE ,  DA COSTA HERVE ,  BENNEJEAN CAROLINE ,  DELAGRANGE PHILIPPE ,  RENARD PIERRE

IPC: C07D333/58 ,  A61K31/235 ,  A61K31/343 ,  A61K31/381 ,  A61K31/4045 ,  A61K31/437 ,  A61P3/04 ,  A61P3/10 ,  A61P15/00 ,  A61P25/00 ,  A61P25/04 ,  A61P25/16 ,  A61P25/20 ,  A61P25/28 ,  A61P35/00 ,  C07C231/12 ,  C07C233/18 ,  C07C233/60 ,  C07D209/08 ,  C07D209/20 ,  C07D307/68 ,  C07D307/79 ,  C07D307/81 ,  C07D333/54 ,  C07D471/04 ,  C07C209/16 ,  A61K31/165 ,  A61K31/335

Abstract: The invention relates to compounds of formula (I): wherein: B represents a hydrogen atom, a COOR group, a CONRR' group, or a (C 1 -C 6 )alkyl group substituted by a COOR, CONRR' or OR group, G 1 represents a -X'-(CH 2 ) n -X-(CH 2 ) m -X''- chain wherein X, X', X'', n and m are as defined in the description, Cy represents a grouping of formula (II) or (III): G 2 represents an alkylene chain as defined in the description, and A represents a NRCOR', NRCSR', CONRR', CSNRR', NRCONR'R'' or NRCSNR'R'' group.

公开(公告)号：AR044245A1

公开(公告)日：2005-09-07

申请号：ARP040101515

申请日：2004-05-04

Applicant: SERVIER LAB

Inventor： GRAINDORGE EMMANUEL ,  FRANCOTTE PIERRE ,  BOVERIE STEPHANE ,  DE TULLIO PASCAL ,  PIROTTE BERNARD ,  CAIGNARD DANIEL-HENRI ,  LESTAGE PIERRE ,  DANOBER LAURENCE ,  RENARD PIERRE

IPC: A61P25/18 ,  C07D513/04 ,  A61K31/549 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  C07D33/00 ,  C07D285/00

Abstract: Compuestos derivados de tiadiazina, procedimientos de preparación, sus enantiómeros, diastereoisómeros y, también sus sales de adición a un ácido o a una base farmacéuticamente aceptables. Estos compuestos son receptores del AMPA y se utilizan en el tratamiento y prevención de trastornos de la memoria. Reivindicación 1: Compuestos de fórmula (1) donde: A forma con los dos átomos de C que lo contienen un grupo tienilo, furilo o pirrolilo elegido entre los grupos de fórmulas (2), donde X representa, respectivamente, un átomo de S, O o de N y Ra, Rb, que pueden ser idénticos o diferentes, independientemente uno de otro, representan un átomo de H, un grupo alquilo C1-6 lineal o ramificado (opcionalmente sustituido por uno o varios átomos de F), un grupo alcoxi C1-6 lineal o ramificado, un átomo de halógeno, un grupo hidroxi, un grupo amino (opcionalmente sustituido por un grupo alquilcarbonilo C1-6 lineal o ramificado, por uno o dos grupos alquilo C1-6 lineal o ramificado), un grupo carboxilo o un grupo alcoxicarbonilo C1-6 lineal o ramificado; un grupo oxatiol elegido entre los grupos de fórmulas (3) donde Ra es el definido anteriormente; un grupo tiazol elegido entre los grupos de fórmulas (4), donde Ra es el definido anteriormente; un grupo isotiazol elegido entre los grupos de fórmulas (5), donde Ra es el definido anteriormente; un grupo oxazol elegido entre los grupos de fórmulas (6), donde Ra es el definido anteriormente; o un grupo imidazol de fórmula (7), donde Ra es el definido anteriormente; la doble línea lisa y punteada representa una unión simple o una unión doble, R1 representa un átomo de H o un grupo alquilo C1-6 lineal o ramificado, opcionalmente sustituido por uno o varios átomos de F, uno o varios átomos de halógeno que no sean F, o un grupo alquilo (C1-6)-alcoxi (C1-6) donde cada parte alquilo puede ser lineal o ramificada, R2 representa un átomo de H o un grupo alquilo C1-6 lineal o ramificado, opcionalmente sustituido por uno o varios átomos de F, o una pluralidad de átomos de halógeno que no sean F, R3 representa un átomo de H o un grupo seleccionado entre alquilo C1-6 lineal o ramificado, CONHR' o SO2NHR' donde R' representa un grupo alquilo C1-6 lineal o ramificado, sus enantiómeros, diastereoisómeros y, también, sus sales de adición a un ácido o a una base farmacéuticamente aceptable.

公开(公告)号：SI1411057T1

公开(公告)日：2005-08-31

申请号：SI200330032

申请日：2003-10-14

Applicant: SERVIER LAB

Inventor： PRUDHOMME MICHELLE ,  HUGON BERNADETTE ,  ANIZON FABRICE ,  HICKMAN JOHN ,  PIERRE ALAIN ,  GOLSTEYN ROY ,  RENARD PIERRE ,  PFEIFFER BRUNO

IPC: A61K31/40 ,  A61K31/407 ,  A61K31/437 ,  A61K31/7056 ,  A61K31/706 ,  A61P35/00 ,  A61P43/00 ,  C07D471/22 ,  C07D487/14 ,  C07D491/14 ,  C07D491/147 ,  C07H19/23

Abstract: (3,4-a:3,4-c) Carbazole derivatives (I), their enantiomers, diastereoisomers and salts with acids and bases. (3,4-a:3,4-c) Carbazole derivatives of formula (I), their enantiomers, diastereoisomers and salts with acids and bases A = ring that is saturated, partially, or fully unsaturated, and that may be aromatic; W' = phenyl or pyridinyl; Z' = U'-V', methylene dioxy or ethylenedioxy; U' = bond, 1-6C alkylene, 2-6C alkenylene, optionally substituted by 1 or 2 halo or OH groups; V' = H, halo, CN, NO2, azido, 1-6C alkyl or alkoxy, aryl, aralkyl, OH, aryloxy, arylalkoxy, formyl, COOH, NH2CO, NR3R4, -C(O)-T1, -C(O)-NR3-T1, NR3C(O)T1, -O-C(O)-T1, -C(O)-OT1, -NR3-T2-NR3R4, -NR3-T2-OR3, -NR3-T2-COOR3, -O-T'2-NR3R4, -O-T'2-OR3, -O-T'2-COOR3, or -S(O)t-R3; R3, R4 = H, 1-6C alkyl, aryl, aralkyl or together form 5-10 membered saturated mono or bicyclic heterocycle, optionally with a second hetero atom (O or N) and optionally substituted by alkyl, aryl, aralkyl, OH, alkoxy, amino mono- or dialkylamino; T1 = alkyl (optionally substituted by -OR3, -NR3R4, -COOR3, -C(O)R3, or -C(O)NR3R4), 2-6C alkenyl, optionally substituted; T2 = 1-6C alkylene; T'2 = 1-6C alkylene optionally substituted by one or more OH groups; t = 0, 1, or 2; Q1 = O or NR2; R2 = H, 1-6C alkyl, aryl, aralkyl, cycloalkyl, cycloalkyl alkyl, -OR3, -NR3R4, -O-T2-NR3R4, NR3-T2-NR3R4, mono- or di-hydroxyalkylamino, -C(O)R3, -NH-C(O)-R3, or 1-6C alkylene optionally substituted by halo, CN, NO2, -OR3, -NR3R4, -COOR3, -C(O)R3, hydroxyalkylamino, dihydroxyalkylamino, -C(O)-NHR3; Q2 = O or NR'2; R'2 = H, 1-6C alkyl, aryl, aralkyl, cycloalkyl, cycloalkyl alkyl, -OR3, -NR3R4, -O-T2-NR3R4, NR3-T2-NR3R4, mono- or di-hydroxyalkylamino, -C(O)R3, -NH-C(O)-R3, or 1-6C alkylene optionally substituted by halo, CN, NO2, -OR3, -NR3R4, -COOR3, -C(O)R3, hydroxyalkylamino, dihydroxyalkylamino, -C(O)-NHR3; X1 = H, OH, alkoxy, mercapto, alkylthio; Y1 = H or X1 and Y1 together form carbonyl or thiocarbonyl; X2 = H, OH, alkoxy, mercapto, alkylthio; Y2 = H or X2 and Y2 together form carbonyl or thiocarbonyl; X'1 = H, OH, alkoxy, mercapto, alkylthio; Y'1 = H or X'1 and Y'1 together form carbonyl or thiocarbonyl; X'2 = H, OH, alkoxy, mercapto, alkylthio; Y'2 = H or X'2 and Y'2 together form carbonyl or thiocarbonyl; R1 = H, 1-6C alkyl (optionally substituted by one or more OH, alkoxy, hydroxyalkoxy, or NR3R4 groups) or it is a group of formula (a); Ra - Rd = a bond, H, halo, OH, alkoxy, aryloxy, arylalkoxy, alkyl, aralkyl, aryl, -NR3R4, azido, -N=NR3, or -O-C(O)-R5; R5 = alkyl optionally substituted by one or more halo, OH, amino, mono- or dialkylamino, aryl, aralkyl, cycloalkyl, or heterocycloalkyl; Re = methylene or -U1-Ra; U1 = a bond or methylene; and n = 0 or 1. with the proviso that the following compounds are not within the scope of (I): 3b, 6a, 6b, 7-tetrahydro-1H-dipyrrolo(3,4-a:3,4-c) carbazole-1,3,4,6(2H, 3aH, 5H)-tetrone; 5-ethyl-3b, 6a, 6b, 7-tetrahydro-1H-dipyrrolo(3,4-a:3,4-c) carbazole-1,3,4,6(2H, 3aH, 5H)-tetrone; 3b, 6a, 7, 11c-tetrahydro-1H-dipyrrolo(3,4-a:3,4-c) carbazole-1,3,4,6(2H, 3aH, 5H)-tetrone; and 3b, 6a, 6b, 7-tetrahydrofuro(3,4a)pyrrolo(3,4-c) carbazole-1,3,4,6(2H, 3aH, 5H)-tetrone.

公开(公告)号：ZA200501010B

公开(公告)日：2005-08-30

申请号：ZA200501010

申请日：2005-02-03

Applicant: SERVIER LAB

Inventor： KOCH MICHEL ,  TILLEQUIN FRANCOIS ,  MICHEL SYLVIE ,  HICKMAN JOHN ,  PIERRE ALAIN ,  LEONCE STEPHANE ,  PFEIFFER BRUNO ,  RENARD PIERRE

IPC: C07D491/147 ,  A61K31/4375 ,  A61K31/4985 ,  A61P35/00 ,  C07B61/00 ,  C07D491/14 ,  C07D491/22 ,  C07D ,  A61K ,  A61P

Abstract: Benzo[b]chromeno[g]naphthyridone or pyrano[2',3':7,8]quinolino[2,3-b]quinoxalinone derivatives (I) are new. Benzo[b]chromeno[g]naphthyridone or pyrano[2',3':7,8]quinolino[2,3-b]quinoxalinone derivatives of formula (I) and their isomers, N-oxides and salts are new: B 1, B 2C or N, at least one being N; X, Y : H, halo, OH, 1-6C alkoxy, NO 2, CN, 1-6C alkyl, 2-6C alkenyl, 1-6C polyhaloalkyl or NR aR b; R a, R bH, COCF 3, CONH 2 or 1-6C alkyl optionally substituted with NR' aR' b or NR aR b is a 5- to 7-membered ring optionally containing another heteroatom (O or N); R' a, R' bH or 1-6C alkyl, or NR' aR' b is a 5- to 7-membered ring optionally containing another heteroatom (O or N); X 1, Y 1X and Y or are absent when B 1, B 2 is N; R 1H or 1-6C alkyl; R 2H, 1-6C alkyl, OR" a, NR' aR' b, OT aOR" a, NR" aT aNR' aR' b, NR" aCOT aH, OCOT aH, OT aNR' aR' b, NR" aT aOR" a, NR" aT aCOOR" a or NR" aCOT aNR' aR' b; T a1-6C alkylene; R" aH or 1-6C alkyl; R 3, R 4H or 1-6C alkyl or together form a 3- to 6-membered ring; A : CHR 5CHR 6, CH=CR 7, CR 7=CH, COCHR 8 or CHR 8CO; R 5, R 6H, OR c, NR cR d, SR c, W 1C(W 2)U'V', W 1C(W 2)W 3T 1, W 1SO nW 3T 1, W 1SO nT 1 or C(W 2)T 1, or together form OC(Z)O, NHC(Z)O, OC(Z)NH, NHC(Z)NH, O(CH 2) mO, OCOB'COO, NHCOB'COO or OCOB'CONH, or CR 5R 6 is an oxirane or optionally N-substituted aziridine group; R c, R dH, 1-6C alkyl, aryl, aryl(1-6C)alkyl or COR e; R eH, aryl or NR"' aR"' b; R"' a, R"' bH or NR"' aR"' b is a 5- to 7-membered ring optionally containing another heteroatom (O or N); W 1O, S or NR c; W 2O or S; U' : 1-8C alkylene or 2-8C alkenylene, or is a bond when W 2 is not O and V' is not H, aryl or NH 2; V' : H, aryl, OR c, COOR c, COR c, CONR' aR' b, NR cR d, N(R c)COOR' c or N(R c)COR' c; R' c1-6C alkyl, aryl or aryl(1-6C)alkyl; W 3O, S or NR c; T 1H, 1-6C alkyl, 2-6C alkenyl, aryl, aryl(1-6C)alkyl, or 1-6C alkyl or 2-6C alkenyl substituted with OR c or NR' aR' b; n : 1 or 2; Z : O or S; m : 1-4; B' : bond, 1-6C alkylene or 2-6C alkenylene; R 7H, OR" a, W 1C(W 2)U'V', W 1C(W 2)W 3T 1, W 1SO nW 3T 1, W 1SO nT 1 or C(W 2)T 1; and R 8H, 2-7C alkanoyloxy or OR" a. An independent claim is also included for the preparation of (I). [Image] ACTIVITY : Cytostatic. cis-1,2-Acetoxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]chromeno[6,5-g][1,8]naphthyridin-7-one had IC50 values of 0.32 mu M against L1210 murine leukemia cells and 0.037 mu M against KB-3-1 human epidermoid carcinoma cells. MECHANISM OF ACTION : Cell cycle blocker.

公开(公告)号：AT301635T

公开(公告)日：2005-08-15

申请号：AT98402963

申请日：1998-11-27

Applicant: SERVIER LAB

Inventor： LEFOULON FRANCOIS ,  DEMUYNCK LUC ,  LESIEUR DANIEL ,  DEPREUX PATRICK ,  BENNEJEAN CAROLINE ,  RENARD PIERRE ,  DELAGRANGE PHILIPPE

IPC: A61K31/00 ,  A61K31/10 ,  A61K31/16 ,  A61K31/165 ,  A61K31/17 ,  A61K31/18 ,  A61K31/34 ,  A61K31/341 ,  A61K31/38 ,  A61K31/381 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4406 ,  A61P25/20 ,  A61P43/00 ,  C07C233/05 ,  C07C233/17 ,  C07C233/18 ,  C07C233/22 ,  C07C233/31 ,  C07C233/36 ,  C07C233/47 ,  C07C233/58 ,  C07C233/60 ,  C07C255/66 ,  C07C275/24 ,  C07C309/65 ,  C07C317/14 ,  C07C317/22 ,  C07C317/32 ,  C07C327/42 ,  C07C335/06 ,  C07D213/56 ,  C07D233/60 ,  C07D307/12 ,  C07D307/52 ,  C07D307/54 ,  C07D333/16 ,  C07D333/20

Abstract: Naphthalenic compounds (I), their enantiomers, diastereoisomers, and salts with acids and bases. The naphthalenic compounds are of formula (I) A and B' rings = naphthalene, 1,2-dihydronaphthalene, 2,3- dihydronaphthalene, 1,4- dihydronaphthalene, or tetrahydronaphthalene; T = 1-6C alkylene which may be substituted by one or more 1-6C alkyl, alkoxy, alkoxycarbonyl, OH, or COOH groups; R = H, OH, R', or OR'; R' = 1-6C alkyl, 2-6C alkenyl or alkynyl, 3-7C cycloalkyl, 4-7C cycloalkenyl, aryl, biphenyl, or heteroaryl (these groups being optionally substituted), or 1-6C trihaloalkyl sulfonyl; R may further link with two atoms of ring A and = a 5-7 membered saturated or unsaturated O-containing ring, which may be substituted by 1-6C alkyl, alkoxy, alkoxy-carbonyl, OH, or oxo; G1 = halo (in which case it is linked to ring B'), 1-6C trihalo alkyl sulfonyloxy, COOH, formyl, CN, R1 or -O-CO-R1; R1 = 1-6C alkyl, 2-6C alkenyl or alkynyl, 3-7C cycloalkyl, aryl, biphenyl, or heteroaryl (these groups being optionally substituted); G2 = a group G20, G21, or G22; X = O or S; R2 = H or 1-6C alkyl; R21 = 1-6C alkyl, 2-6C alkenyl or alkynyl, 3-7C cycloalkyl, aryl, biphenyl, or heteroaryl (these groups being optionally substituted) with various provisos listed in the Definitions section.

公开(公告)号：FR2865734A1

公开(公告)日：2005-08-05

申请号：FR0400988

申请日：2004-02-03

Applicant: SERVIER LAB

Inventor： KOCH MICHEL ,  TILLEQUIN FRANCOIS ,  MICHEL SYLVIE ,  HICKMAN JOHN ,  PIERRE ALAIN ,  LEONCE STEPHANE ,  PFEIFFER BRUNO ,  RENARD PIERRE

IPC: C07D491/147 ,  A61K31/4375 ,  A61K31/4985 ,  A61P35/00 ,  C07B61/00 ,  C07D491/14 ,  C07D491/22 ,  A61K31/436

Abstract: Benzo[b]chromeno[g]naphthyridone or pyrano[2',3':7,8]quinolino[2,3-b]quinoxalinone derivatives (I) are new. Benzo[b]chromeno[g]naphthyridone or pyrano[2',3':7,8]quinolino[2,3-b]quinoxalinone derivatives of formula (I) and their isomers, N-oxides and salts are new: B 1, B 2C or N, at least one being N; X, Y : H, halo, OH, 1-6C alkoxy, NO 2, CN, 1-6C alkyl, 2-6C alkenyl, 1-6C polyhaloalkyl or NR aR b; R a, R bH, COCF 3, CONH 2 or 1-6C alkyl optionally substituted with NR' aR' b or NR aR b is a 5- to 7-membered ring optionally containing another heteroatom (O or N); R' a, R' bH or 1-6C alkyl, or NR' aR' b is a 5- to 7-membered ring optionally containing another heteroatom (O or N); X 1, Y 1X and Y or are absent when B 1, B 2 is N; R 1H or 1-6C alkyl; R 2H, 1-6C alkyl, OR" a, NR' aR' b, OT aOR" a, NR" aT aNR' aR' b, NR" aCOT aH, OCOT aH, OT aNR' aR' b, NR" aT aOR" a, NR" aT aCOOR" a or NR" aCOT aNR' aR' b; T a1-6C alkylene; R" aH or 1-6C alkyl; R 3, R 4H or 1-6C alkyl or together form a 3- to 6-membered ring; A : CHR 5CHR 6, CH=CR 7, CR 7=CH, COCHR 8 or CHR 8CO; R 5, R 6H, OR c, NR cR d, SR c, W 1C(W 2)U'V', W 1C(W 2)W 3T 1, W 1SO nW 3T 1, W 1SO nT 1 or C(W 2)T 1, or together form OC(Z)O, NHC(Z)O, OC(Z)NH, NHC(Z)NH, O(CH 2) mO, OCOB'COO, NHCOB'COO or OCOB'CONH, or CR 5R 6 is an oxirane or optionally N-substituted aziridine group; R c, R dH, 1-6C alkyl, aryl, aryl(1-6C)alkyl or COR e; R eH, aryl or NR"' aR"' b; R"' a, R"' bH or NR"' aR"' b is a 5- to 7-membered ring optionally containing another heteroatom (O or N); W 1O, S or NR c; W 2O or S; U' : 1-8C alkylene or 2-8C alkenylene, or is a bond when W 2 is not O and V' is not H, aryl or NH 2; V' : H, aryl, OR c, COOR c, COR c, CONR' aR' b, NR cR d, N(R c)COOR' c or N(R c)COR' c; R' c1-6C alkyl, aryl or aryl(1-6C)alkyl; W 3O, S or NR c; T 1H, 1-6C alkyl, 2-6C alkenyl, aryl, aryl(1-6C)alkyl, or 1-6C alkyl or 2-6C alkenyl substituted with OR c or NR' aR' b; n : 1 or 2; Z : O or S; m : 1-4; B' : bond, 1-6C alkylene or 2-6C alkenylene; R 7H, OR" a, W 1C(W 2)U'V', W 1C(W 2)W 3T 1, W 1SO nW 3T 1, W 1SO nT 1 or C(W 2)T 1; and R 8H, 2-7C alkanoyloxy or OR" a. An independent claim is also included for the preparation of (I). [Image] ACTIVITY : Cytostatic. cis-1,2-Acetoxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]chromeno[6,5-g][1,8]naphthyridin-7-one had IC50 values of 0.32 mu M against L1210 murine leukemia cells and 0.037 mu M against KB-3-1 human epidermoid carcinoma cells. MECHANISM OF ACTION : Cell cycle blocker.

公开(公告)号：CA2493090A1

公开(公告)日：2005-08-03

申请号：CA2493090

申请日：2005-01-13

Applicant: SERVIER LAB

Inventor： PIERRE ALAIN ,  LEONCE STEPHANE ,  PFEIFFER BRUNO ,  RENARD PIERRE ,  TILLEQUIN FRANCOIS ,  KOCH MICHEL ,  MICHEL SYLVIE ,  HICKMAN JOHN

IPC: C07D491/147 ,  A61K31/4375 ,  A61K31/4985 ,  A61P35/00 ,  C07B61/00 ,  C07D491/14 ,  C07D491/22 ,  C07D493/14 ,  A61K31/498

Abstract: Composés de formule (I): (voir formule I) dans laquelle: .cndot. B1, B2 représentent un atome de carbone ou d'azote, .cndot. X, Y, X1 et Y1 représentent un groupement choisi parmi hydrogène, halogène, hydroxy, alkoxy, nitro, cyano, trihalogénoalkyle et NR a R b dans lequel R a et R b sont tels que définis dans la description, .cndot. R1 représente un atome d'hydrogène ou un groupement alkyle, .cndot. R2 représente un groupement choisi parmi atome d'hydrogène, alkyle, - OR'a, -NR'a R'b, -O-T a-OR"a, -NR"a-T a-NR'a R'b, NR"a-C(O)-T a H, -O-C(O)-T a H, -O-T a-NR a'R b', -NR"a-T a-OR"a, -NR"a-T a-CO2R"a, -NR"a-C(O)-T a-NR'a R'b dans lesquels R'a, R'b, R"a et T a sont tels que définis dans la description, .cndot. R3, R4 représentent un atome d'hydrogène ou un groupement alkyle, .cndot. A représente un groupement de formule -CH(R5)-CH(R6)-, -CH=C(R7)-, -C(R7)=CH-, -C(O)CH(R8)-, -CH(R8)-C(O)- dans lesquelles R5, R6, R7 et R8 son t tels que définis dans la description, leurs isomères définis dans la description, N-oxydes, ainsi que leurs sels d'addition à un acide ou à une base pharmaceutiquement acceptable. Médicaments.

公开(公告)号：BR0314878A

公开(公告)日：2005-08-02

申请号：BR0314878

申请日：2003-10-17

Applicant: SERVIER LAB

Inventor： COUDERT GERARD ,  AYERBE NATHALIE ,  LEPIFRE FRANK ,  ROUTIER SYLVAIN ,  CAIGNARD DANIEL HENRI ,  RENARD PIERRE ,  HICKMAN JOHN ,  PIERRE ALAIN ,  LEONCE STEPHANE

IPC: A61P35/00 ,  C07D471/14 ,  C07D487/04 ,  C07D491/14 ,  C07D491/147 ,  C07D491/22 ,  C07D498/14 ,  C07D498/22 ,  A61K31/5365

Abstract: 1,4-benzodioxino(2,3-e)isoindole derivatives (I) are new. 1,4-benzodioxino(2,3-e)isoindole derivatives of formula (I) and their enantiomers, diastereoisomers, N-oxides and addition salts with acids and bases are new. A = atoms that complete groups of formula (a) or (b); W1 = atoms that complete a phenyl or pyridyl ring; Z' = H, halogen, 1-6C alkyl or alkoxy (both optionally substituted by aryl), nitro, cyano, hydroxy, aryl, or NR5R6; R5, R6 = H or 1-6C alkyl; R4 = H, 1-6C alkyl, aryl, aryl(1-6C)alkyl or COOR'5; R'5 = 1-6C alkyl, aryl or aryl(1-6C)alkyl; Y' = oxygen or methylene; R2 = H; and R3 = H, 1-6C alkyl, aryl, aryl(1-6C)alkyl or trifluoromethylsulfonyl; or R2+R3 = bond; R1 = H, 1-6C alkyl, aryl, aryl(1-6C)alkyl, or 1-6C alkylene, substituted by one or more of OR5 or NR5R6; Z1, Z2 = H or; Z1+Z2 = fused phenyl; and aryl = phenyl, naphthyl, di- or tetra-hydronaphthyl, indenyl or indanyl (all optionally substituted by one or more of halo, 1-6C (trihalo)alkyl or alkoxy, hydroxy, amino or mono- or di-1-6C alkylamino. Provided that if Z' is H, then R1 is not H. Independent claims are included for preparing (I).

公开(公告)号：NZ532365A

公开(公告)日：2005-07-29

申请号：NZ53236502

申请日：2002-10-21

Applicant: SERVIER LAB

Inventor： PRUDHOMME MICHELLE ,  MARMINON CHRISTELLE ,  MOREAU PASCALE ,  HICKMAN JOHN ,  PIERRE ALAIN ,  BIZOT-ESPIARD JEAN-GUY ,  PFEIFFER BRUNO ,  RENARD PIERRE

IPC: A61K31/7056 ,  A61P3/04 ,  A61P3/10 ,  A61P25/00 ,  A61P25/16 ,  A61P25/28 ,  A61P35/00 ,  A61P43/00 ,  C07H19/23

Abstract: Hydroxyalkyl indolocarbazole compounds of formula (I), their isomers and their addition salts with a pharmaceutically acceptable acid or base that have a selective inhibitory activity in respect of glycogen synthesis kinase (GSK-3) are disclosed, wherein: R1 and R2 each represent a group selected among hydrogen, C1-C6alkyl, arylC1-C6alkyl, hydroxy, C1-C6hydroxylalkyl, dihydroxyC1-C6alkyl, C1-C6alkoxy, alkoxyC1-C6alkyl, amino and C1-C6aminoalkyl (optionally substituted); Ra and Rb each represent an C1-C6alkylene chain; X1 , X2 and X3 each represent a group selected among hydroxy, C1-C6alkoxy, aryloxy, arylC1-C6alkoxy, C1-C6alkyl, amino (optionally substituted), halogen, C1-C6alkylcarbonyloxy and azido; X4 represents a methylidene group or a group of formula -Rc-X1, wherein Rc represents a single bond or a methylene group and X1 is as defined above.

公开(公告)号：FR2865474A1

公开(公告)日：2005-07-29

申请号：FR0400689

申请日：2004-01-26

Applicant: SERVIER LAB

Inventor： FRANCOTTE PIERRE ,  FRAIKIN PIERRE ,  DE TULLIO PASCAL ,  PIROTTE BERNARD ,  LESTAGE PIERRE ,  DANOBER LAURENCE ,  CAIGNARD DANIEL HENRI ,  RENARD PIERRE

IPC: A61K31/5415 ,  A61K31/549 ,  A61P9/10 ,  A61P25/00 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07B53/00 ,  C07D285/22 ,  C07D285/24 ,  A61P25/18

Abstract: 4-(Fluorinated alkyl or fluorinated cycloalkylalkyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxide derivatives (I) are new. Benzothiadiazine derivatives of formula (I) (including optical isomers where appropriate) and their acid or base addition salts are new. R fmono- or polyfluoroalkyl or mono- or polyfluoro-cycloalkylalkyl; R 1H, alkylaminocarbonyl or alkyl (optionally substituted by one or more halo); R 2H, halo, cycloalkyl or alkyl (optionally substituted by one or more halo); R 3 - R 6H, halo, NO 2, CN, alkylsulfonyl, OH, alkoxy, alkyl (optionally substituted by one or more halo) or NH 2 (optionally substituted by 1 or 2 alkyl); Alkyl moieties have 1-6C and cycloalkyl moieties 3-7C; provided that R 3 = H when R 6 is other than H. Independent claims are also included for: (A) new benzothiadiazine derivatives of formula (VI); and (B) the preparation of (I). [Image] [Image] ACTIVITY : Nootropic; Tranquilizer; Antidepressant; Neuroprotective; Antiparkinsonian; Anticonvulsant; Neuroleptic. In object recognition tests in 17 month old rats, 7-chloro-4-(2-fluoroethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxide (Ia) at oral doses of 0.1 mg/kg significant reduced age-associated loss of memory. MECHANISM OF ACTION : alpha -Amino-5-methyl-4-isoxazole-propionic acid (AMPA) receptor modulator. In tests in Xenopus ovocytes, (Ia) strongly potentiated the excitative effect of AMPA, showing EC2X and EC5X values of 6.7 mu M and 14.5 mu M respectively for increasing the AMPA-inducedionic current.