公开(公告)号：FR2819512A1

公开(公告)日：2002-07-19

申请号：FR0100639

申请日：2001-01-18

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  LE DIGUARHER THIERRY ,  DOREY GILBERT ,  HICKMAN JOHN ,  PIERRE ALAIN ,  TUCKER GORDON ,  GUILBAUD NICOLAS ,  FAUCHERE JEAN LUC ,  ORTUNO JEAN CLAUDE

IPC: A61P35/00 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/06 ,  A61K31/55

Abstract: N-Substituted cyclo (d)-fused bicyclic azepane or azepanone derivatives (I) are new. Bicyclic azepane derivatives of formula (I) and their enantiomers, diastereomers and acid or base addition salts are new. W = CO or CH2; X = direct bond, alkylene, CO, S(O)n, S(O)n-A1, CO-A1, A1-S(O)n-A1 or A1-CO-A1 (bonded to the ring at the left-hand terminal); A1 = alkylene; n = 0-2; Y = aryl, heteroaryl, cycloalkyl or heterocycloalkyl (all optionally substituted (os) by R6); R1, R2 = H or as for Y; or together form a bond; T = CHR3, NR3 or NR3CO (bonded to the ring at the left-hand terminal); R3 = H; or alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl (all os by one or more R5); V = H; or aryl or heteroaryl (both os by one or more R5); A2 = -(CR4R'4)p; p = 0-4 (but not 0 if T = NR3); R4, R'4 = H, alkyl (os by R7), alkenyl, alkynyl or R7; R7 = OR3, NR3R'3, S(O)nR3, CONR3R'3, NR3COR'3, NR3SO2R'3, SO2NR3R'3 or NR3COOR'3; R'3 = as R3; R5 = halo, alkyl, alkoxy, OH, SH, alkylthio, CN, NH2 (os by 1 or 2 alkyl), NO2, COOH, alkoxycarbonyl, CONH2 (os by 1 or 2 alkyl), carbamoyl, os aryl, os aralkyl, os heteroaryl, os heteroaralkyl, os cycloalkyl, os cycloalkylalkyl, os heterocycloalkyl or os heterocycloalkylalkyl; R6 = halo, =O, OH, CN, NO2, COOH, alkoxycarbonyl, U-R60 or A60-U-R60; A60 = alkylene; U = direct bond, O, NH, S(O)n, NHCO, CONH, SO2NH or NHSO2; R60 = alkyl, aryl, aralkyl, heteroaryl or heteroarylalkyl; B' = group completing an optionally partially hydrogenated aryl or heteroaryl group (os by one or more of CN, alkyl, alkoxy, OH or halo); alkyl or alkylene moieties have 1-6C; cycloalkyl moieties have 3-8C; heterocycloalkyl moieties are 5-7 membered and contain 1-3 of N, O and S as heteroatom(s); aryl moieties are phenyl or naphthyl; heteroaryl moieties are mono- or bicyclic 5-11 membered systems containing at least one aromatic ring and 1-5 of N, O and S as heteroatom(s); the substituents in os aryl, heteroaryl, aralkyl or heteroaralkyl are one or more of CN, alkylcarbonyl, CONH2 (os by 1 or 2 alkyl) or halo (in the ring part); the substituents in os cycloalkyl, heterocycloalkyl, cycloalkylalkyl or heterocycloalkylalkyl are one or more of =O, CN, alkylcarbonyl, CONH2 (os by 1 or 2 alkyl) or halo (in the ring part). An Independent claim is included for the preparation of (I).

公开(公告)号：EA199900865A3

公开(公告)日：2000-10-30

申请号：EA199900865

申请日：1999-10-22

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  DOREY GILBERT ,  LESTAGE PIERRE ,  LOCKHART BRIAN

IPC: C07D215/06 ,  A61K31/47 ,  A61K31/497 ,  A61K31/517 ,  A61P9/10 ,  A61P25/00 ,  A61P25/08 ,  A61P25/16 ,  A61P25/28 ,  A61P27/12 ,  A61P43/00 ,  C07D215/20 ,  C07D221/20 ,  C07D401/06 ,  C07D471/10

Abstract: Соединениеобщейформулы (I)где Rпредставляетсобойатомводородаилигруппугде A являетсятаким, какопределенов описании,Rи R, каждыйнезависимо, представляютсобойалкил, циклоалкил, гетероциклоалкил, необязательнозамещенныйарил, необязательнозамещенныйгетероарил, циклоалкилалкил, гетероциклоалкилалкил, необязательнозамещенныйарилалкил, необязательнозамещенныйгетероарилалкилилинеобязательнозамещенныйаминоалкилилиRи Rвместесосвязывающимихатомомуглеродаобразуютциклоалкильнуюилимоноциклическуюгетероциклическуюгруппу, замещеннуюилинезамещенную,Rпредставляетсобойатомводородаилигруппу, выбраннуюизнеобязательнозамещенногоалкила, необязательнозамещенногоалкенилаи необязательнозамещенногоалкинила, илигруппу Q или - V-Q-, где V представляетсобойгруппуалкилена, алкениленаилиалкиниленаи Q представляетсобойнеобязательнозамещеннуюциклоалкильнуюгруппу, необязательнозамещеннуюарильнуюгруппу, необязательнозамещеннуюгетероциклоалкильнуюгруппуилинеобязательнозамещеннуюгетероарильнуюгруппу,Rи Rобразуютвместесвязьиликаждыйпредставляетсобойатомводорода,R, R, Rи Rкаждыйнезависимопредставляетсобойатомводорода, атомгалогена, алкильнуюгруппу, (C-C)циклоалкильнуюгруппуилигруппу -OW, где W являетсятаким, какопределенов описании.

公开(公告)号：NO322100B1

公开(公告)日：2006-08-14

申请号：NO20020262

申请日：2002-01-17

Applicant: SERVIER LAB

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

IPC: C07C317/00 ,  C07D233/61 ,  A61K31/41 ,  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 ,  C07D233/64 ,  C07D401/06

Abstract: Compound of formula (I):wherein:X represents a bond or alkylene, CO, S(O)n, -S(O)n-A1-, -CO-A1-, -A-S(O)n-A'1- or -A1-CO-A'1-,Y represents aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each unsubstituted or substituted,R1, R2, R3 and R4 each independently of the others represent hydrogen or aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each unsubstituted or substituted,or R1, R2, R3 and R4, taken in pairs, together form a bond, or form a fused benzene ring or a fused aromatic or partially unsaturated heterocycle,T represents -CH(R5)-, -N(R5)- or -N(R5)CO-,V represents hydrogen or unsubstituted or substituted aryl or heteroaryl,A2 represents [C(R6)(R'6)]p,R7 and R8 are as defined in the description,their isomers and addition salts thereof with a pharmaceutically acceptable acid or base and medicinal products containing the same are useful as farnesyl transferase inhibitors.

公开(公告)号：PT995743E

公开(公告)日：2003-07-31

申请号：PT99402624

申请日：1999-10-22

Applicant: SERVIER LAB

Inventor： LESTAGE PIERRE ,  LOCKHART BRIAN ,  CASARA PATRICK ,  DOREY GILBERT

IPC: C07D215/06 ,  A61K31/47 ,  A61K31/497 ,  A61K31/517 ,  A61P9/10 ,  A61P25/00 ,  A61P25/08 ,  A61P25/16 ,  A61P25/28 ,  A61P27/12 ,  A61P43/00 ,  C07D215/20 ,  C07D221/20 ,  C07D401/06 ,  C07D471/10 ,  C07D401/10 ,  C07D403/06 ,  C07D409/06 ,  C07D401/04 ,  C07D263/44 ,  C07D233/86 ,  A61K31/675

Abstract: Dihydro- and tetrahydro-quinoline derivatives (I) are new. Dihydro- and tetrahydro-quinoline derivatives of formula (I) and their acid or base addition salts are new. R1 = H or a group of formula (i); A = H or -B'NZ1Z2; B' = 1-6C alkylene; Z1, Z2 = H, alkyl, 3-8C cycloalkyl or optionally substituted aryl; or NZ1Z2 = heterocycloalkyl or heteroaryl (optionally substituted); R2, R3 = alkyl, 3-8C cycloalkyl, heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl or aminoalkyl (optionally substituted on N with 1 or 2 alkyl, cycloalkyl, aryl or arylalkyl); or R2 + R3 = form with C of quinoline, 3-8C cycloalkyl or heterocycloalkyl (optionally substituted with alkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl); R40 = alkyl, 2-6C alkenyl, 2-6C alkynyl (all optionally substituted), H, Q or -V'-Q; V' = 1-6C alkylene, 2-6C alkenylene or 2-6C alkynylene; Q = 3-8C cycloalkyl, aryl, heterocycloalkyl, heteroaryl (all optionally substituted); R5, R41 = H; or R5 + R41 = bond; R6-R9 = H, halo, alkyl, 3-8C cycloalkyl or -OW'; W' = aryl, heteroaryl, arylalkyl, heteroarylalkyl (all optionally substituted), H, alkyl, acyl, 3-8C cycloalkyl or heterocycloalkyl; alkyl = 1-6C; aryl = phenyl, naphthyl or biphenyl; heterocycloalkyl = partially unsaturated 4- to 11-membered mono- or bi-cyclic ring containing 1-6 N, S or O; heteroaryl = aromatic or partially aromatic 4- to 11-membered mono- or bi-cyclic ring containing 1-6 N, S or O; substituted aryl, arylalkyl = aryl or arylalkyl substituted with at least one halo, alkyl, 1-6C alkoxy, 1-6C perhaloalkyl, amino (optionally substituted by 1 or 2 alkyl), CN, carboxy, 1-6C alkoxycarbonyl, aminocarbonyl (optionally substituted with 1 or 2 alkyl on N), nitro or OH; substituted alkyl, alkenyl, alkynyl and cycloalkyl = alkyl, alkenyl, alkynyl and cycloalkyl substituted with at least one OH, 1-6C alkoxy, 1-6C alkylthio, amino (optionally substituted with 1 or 2 alkyl), carboxy, nitro, CN, 1-6C alkoxycarbonyl or aminocarbonyl (optionally substituted with 1 or 2 alkyl on N); substituted heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl = heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl substituted with at least one halo, alkyl, 1-6C alkoxy, 1-6C perhaloalkyl, amino (optionally substituted with 1 or 2 alkyl), CN, carboxy, 1-6C alkoxycarbonyl, aminocarbonyl (optionally substituted with 1 or 2 alkyl on N), nitro, OH or oxo; and provided that R6-R9 are not all H and at least one of R6-R9 is -OW', that R2 and R3 are alkyl when R6-R9 are H, alkyl, alkoxy, R41 and R5 form a bond, R40 is other than H or alkyl; when (I) has one OH and R40 is other than H; when (I) has one methoxy and R40 is other than hydroxyalkyl; and (I) is other than 7-methoxy-2,2-diphenyl-1,2-dihydroquinoline. An Independent claim is also included for the preparation of (I).

公开(公告)号：NZ516684A

公开(公告)日：2003-06-30

申请号：NZ51668402

申请日：2002-01-17

Applicant: SERVIER LAB

Inventor： CASARA PATRIC ,  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 ,  C07D233/88 ,  A61K31/44 ,  A61K31/444

Abstract: Compounds of formula (I); where: X is a bond, alkylene, CO, S(O)n, *-S(O)n-A1-, *-CO-A1-, -A1-S(O)n-A'1- or -A1-CO-A'1 (where A1 and A'1 independently represent an alkylene group, and n is 0, 1 or 2), the symbol "*" indicating the point of attachment of those groups to the cycloheptene; Y is an optionally substituted aryl, heteroaryl, cycloalkyl or heterocycloalkyl group; R1, R2, R3 and R4 are independently hydrogen, or optionally substituted aryl, heteroaryl, cycloalkyl or heterocycloalkyl; or R1 and R2, or R2 and R3, or R3 and R4, taken in pairs, together form a bond; or R1 and R2, or R2 and R3, or R3 and R4, taken in pairs with the carbon atoms to which they are bonded, form a fused benzene ring or a fused aromatic or partially unsaturated heterocycle, having 5 or 6 ring members and containing 1 or 2 heteroatoms selected from nitrogen, oxygen and sulfur, on the understanding that only one ring can be fused on the 7-membered structure; T is ?H(R5)-, -N(R5)- or *-N(R5)CO- (where R5 is a hydrogen atom or is an optionally substituted alkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl group) , the symbol "*" indicating the point of attachment of this group to the cycloheptene; V is hydrogen or is an optionally substituted aryl or heteroaryl group; A2 is a [C(R6)(R'6)]p group where p is 0, 1, 2, 3 or 4 when T represents a -CH(R5)- or *-N(R5)CO- group, or p is 1, 2, 3 or 4 when T represents an -N(R5)- group. Pharmaceutical compositions comprising the compound of formula (I) are also described.

公开(公告)号：DE69906445D1

公开(公告)日：2003-05-08

申请号：DE69906445

申请日：1999-10-22

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  DOREY GILBERT ,  LESTAGE PIERRE ,  LOCKHART BRIAN

IPC: C07D215/06 ,  A61K31/47 ,  A61K31/497 ,  A61K31/517 ,  A61P9/10 ,  A61P25/00 ,  A61P25/08 ,  A61P25/16 ,  A61P25/28 ,  A61P27/12 ,  A61P43/00 ,  C07D215/20 ,  C07D221/20 ,  C07D401/06 ,  C07D471/10

Abstract: Dihydro- and tetrahydro-quinoline derivatives (I) are new. Dihydro- and tetrahydro-quinoline derivatives of formula (I) and their acid or base addition salts are new. R1 = H or a group of formula (i); A = H or -B'NZ1Z2; B' = 1-6C alkylene; Z1, Z2 = H, alkyl, 3-8C cycloalkyl or optionally substituted aryl; or NZ1Z2 = heterocycloalkyl or heteroaryl (optionally substituted); R2, R3 = alkyl, 3-8C cycloalkyl, heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl or aminoalkyl (optionally substituted on N with 1 or 2 alkyl, cycloalkyl, aryl or arylalkyl); or R2 + R3 = form with C of quinoline, 3-8C cycloalkyl or heterocycloalkyl (optionally substituted with alkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl); R40 = alkyl, 2-6C alkenyl, 2-6C alkynyl (all optionally substituted), H, Q or -V'-Q; V' = 1-6C alkylene, 2-6C alkenylene or 2-6C alkynylene; Q = 3-8C cycloalkyl, aryl, heterocycloalkyl, heteroaryl (all optionally substituted); R5, R41 = H; or R5 + R41 = bond; R6-R9 = H, halo, alkyl, 3-8C cycloalkyl or -OW'; W' = aryl, heteroaryl, arylalkyl, heteroarylalkyl (all optionally substituted), H, alkyl, acyl, 3-8C cycloalkyl or heterocycloalkyl; alkyl = 1-6C; aryl = phenyl, naphthyl or biphenyl; heterocycloalkyl = partially unsaturated 4- to 11-membered mono- or bi-cyclic ring containing 1-6 N, S or O; heteroaryl = aromatic or partially aromatic 4- to 11-membered mono- or bi-cyclic ring containing 1-6 N, S or O; substituted aryl, arylalkyl = aryl or arylalkyl substituted with at least one halo, alkyl, 1-6C alkoxy, 1-6C perhaloalkyl, amino (optionally substituted by 1 or 2 alkyl), CN, carboxy, 1-6C alkoxycarbonyl, aminocarbonyl (optionally substituted with 1 or 2 alkyl on N), nitro or OH; substituted alkyl, alkenyl, alkynyl and cycloalkyl = alkyl, alkenyl, alkynyl and cycloalkyl substituted with at least one OH, 1-6C alkoxy, 1-6C alkylthio, amino (optionally substituted with 1 or 2 alkyl), carboxy, nitro, CN, 1-6C alkoxycarbonyl or aminocarbonyl (optionally substituted with 1 or 2 alkyl on N); substituted heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl = heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl substituted with at least one halo, alkyl, 1-6C alkoxy, 1-6C perhaloalkyl, amino (optionally substituted with 1 or 2 alkyl), CN, carboxy, 1-6C alkoxycarbonyl, aminocarbonyl (optionally substituted with 1 or 2 alkyl on N), nitro, OH or oxo; and provided that R6-R9 are not all H and at least one of R6-R9 is -OW', that R2 and R3 are alkyl when R6-R9 are H, alkyl, alkoxy, R41 and R5 form a bond, R40 is other than H or alkyl; when (I) has one OH and R40 is other than H; when (I) has one methoxy and R40 is other than hydroxyalkyl; and (I) is other than 7-methoxy-2,2-diphenyl-1,2-dihydroquinoline. An Independent claim is also included for the preparation of (I).

公开(公告)号：FR2819512B1

公开(公告)日：2003-02-21

申请号：FR0100639

申请日：2001-01-18

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  LE DIGUARHER THIERRY ,  DOREY GILBERT ,  HICKMAN JOHN ,  PIERRE ALAIN ,  TUCKER GORDON ,  GUILBAUD NICOLAS ,  FAUCHERE JEAN LUC ,  ORTUNO JEAN CLAUDE

IPC: A61P35/00 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/06 ,  A61K31/55

公开(公告)号：AU2002231886A1

公开(公告)日：2002-07-30

申请号：AU2002231886

申请日：2002-01-16

Applicant: SERVIER LAB

Inventor： FAUCHERE JEAN-LUC ,  CASARA PATRICK ,  GUILBAUD NICOLAS ,  PIERRE ALAIN ,  DOREY GILBERT ,  TUCKER GORDON ,  ORTUNO JEAN-CLAUDE ,  HICKMAN JOHN ,  DIGUARHER THIERRY LE

IPC: A61P35/00 ,  C07D401/14 ,  C07D403/12 ,  C07D413/12 ,  A61K31/415 ,  C07D211/00 ,  C07D223/00 ,  C07D233/00 ,  C07D261/00 ,  C07D401/12

公开(公告)号：ZA200200471B

公开(公告)日：2002-07-22

申请号：ZA200200471

申请日：2002-01-18

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  DIGUARHER THIERRY LE ,  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 ,  C07D ,  A61K

Abstract: Compound of formula (I):wherein:X represents a bond or alkylene, CO, S(O)n, -S(O)n-A1-, -CO-A1-, -A-S(O)n-A'1- or -A1-CO-A'1-,Y represents aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each unsubstituted or substituted,R1, R2, R3 and R4 each independently of the others represent hydrogen or aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each unsubstituted or substituted,or R1, R2, R3 and R4, taken in pairs, together form a bond, or form a fused benzene ring or a fused aromatic or partially unsaturated heterocycle,T represents -CH(R5)-, -N(R5)- or -N(R5)CO-,V represents hydrogen or unsubstituted or substituted aryl or heteroaryl,A2 represents [C(R6)(R'6)]p,R7 and R8 are as defined in the description,their isomers and addition salts thereof with a pharmaceutically acceptable acid or base and medicinal products containing the same are useful as farnesyl transferase inhibitors.

公开(公告)号：EA199900865A2

公开(公告)日：2000-04-24

申请号：EA199900865

申请日：1999-10-22

Applicant: SERVIER LAB

Inventor： CASARA PATRICK ,  DOREY GILBERT ,  LESTAGE PIERRE ,  LOCKHART BRIAN

IPC: C07D215/06 ,  A61K31/47 ,  A61K31/497 ,  A61K31/517 ,  A61P9/10 ,  A61P25/00 ,  A61P25/08 ,  A61P25/16 ,  A61P25/28 ,  A61P27/12 ,  A61P43/00 ,  C07D215/20 ,  C07D221/20 ,  C07D401/06 ,  C07D471/10

Abstract: Соединениеобщейформулы (I)где Rпредставляетсобойатомводородаилигруппугде A являетсятаким, какопределенов описании,Rи R, каждыйнезависимо, представляютсобойалкил, циклоалкил, гетероциклоалкил, необязательнозамещенныйарил, необязательнозамещенныйгетероарил, циклоалкилалкил, гетероциклоалкилалкил, необязательнозамещенныйарилалкил, необязательнозамещенныйгетероарилалкилилинеобязательнозамещенныйаминоалкилилиRи Rвместесосвязывающимихатомомуглеродаобразуютциклоалкильнуюилимоноциклическуюгетероциклическуюгруппу, замещеннуюилинезамещенную,Rпредставляетсобойатомводородаилигруппу, выбраннуюизнеобязательнозамещенногоалкила, необязательнозамещенногоалкенилаи необязательнозамещенногоалкинила, илигруппу Q или - V-Q-, где V представляетсобойгруппуалкилена, алкениленаилиалкиниленаи Q представляетсобойнеобязательнозамещеннуюциклоалкильнуюгруппу, необязательнозамещеннуюарильнуюгруппу, необязательнозамещеннуюгетероциклоалкильнуюгруппуилинеобязательнозамещеннуюгетероарильнуюгруппу,Rи Rобразуютвместесвязьиликаждыйпредставляетсобойатомводорода,R, R, Rи Rкаждыйнезависимопредставляетсобойатомводорода, атомгалогена, алкильнуюгруппу, (C-C)циклоалкильнуюгруппуилигруппу -OW, где W являетсятаким, какопределенов описании.