公开(公告)号：JP2002356486A

公开(公告)日：2002-12-13

申请号：JP2002114443

申请日：2002-04-17

Applicant: SERVIER LAB

Inventor： LAVIELLE GILBERT ,  DUBUFFET THIERRY ,  MULLER OLIVIER ,  MILLAN MARK ,  DEKEYNE ANNE ,  BROCCO MAURICETTE

IPC: A61K31/519 ,  A61P1/14 ,  A61P15/10 ,  A61P15/12 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07D471/00 ,  C07D471/04 ,  C07D491/048 ,  C07D491/052 ,  C07D513/00 ,  C07D519/00

Abstract: PROBLEM TO BE SOLVED: To provide a medicine useful for treatment of depression, impulsive behavioral disorder, anxiety, schizophrenia, Parkinson's disease, dysgnosia, libido dysfunction, sexual dysfunction, appetite disorder and somnipathy due to α2 /5-HT2c antagonist characteristics possessed thereby. SOLUTION: This compound is represented by the formula (I) [wherein, R1 , R2 , R3 and R4 denote each hydrogen atom or the like; X denotes oxygen atom or the like; A denotes a linear or a branched (1-6C) alkylene chain; ring-B denotes an unsaturated nitrogen-containing heterocyclic ring; and R5 denotes a linear or a branched (1-6C) alkyl chain], its enantiomer and diastereoisomer and its addition salt with a pharmaceutically acceptable acid or base. The method for preparing the same and the pharmaceutical composition comprising the same are provided.

公开(公告)号：BRPI1002409A2

公开(公告)日：2012-05-15

申请号：BRPI1002409

申请日：2010-07-20

Applicant: SERVIER LAB

Inventor： NANTEUIL GUILLAUME DE ,  CIMETIERE BERNARD ,  DEKEYNE ANNE ,  MILLAN MARK

IPC: C07D491/052 ,  A61K31/275 ,  A61P25/18

公开(公告)号：NZ586855A

公开(公告)日：2011-11-25

申请号：NZ58685510

申请日：2010-07-16

Applicant: SERVIER LAB

Inventor： DE NANTEUIL GUILLAUME ,  CIMETIERE BERNARD ,  DEKEYNE ANNE ,  MILLAN MARK

IPC: C07D493/04 ,  A61P25/18 ,  C07D497/04

Abstract: Disclosed are compounds of formula (I) e.g. (3aS,9bR)-2-[2-(trans-4-aminocyclohexyl)ethyl]-1,2,3,3a,4,9b-hexahydrochromeno[3,4-c]pyrrole-8-carbonitrile wherein R1 and R2 are defined in the specification, their enantiomers, their diastereoisomers, and also addition salts thereof with a pharmaceutically acceptable acid or base for use in the treatment or prevention of schizophrenia and other psychoses, abuse of drugs, as anxious states and toxicomania, the treatment of bipolar depressive states, impulsive behaviours such as obsessivecompulsive aggressiveness, treatment of Parkinson's disease, memory and other cognitive disorders associated with psychiatric and neurological diseases such as dementias and Alzheimer's disease, adolescents, the treatment of pain, nausea, premature ejaculation and also for renal protection. Also disclosed is a process for the preparation of said compounds characterised in that there is used as starting material bicyclo[2.2.2]oct-5-ene-2-carbonitrile which is subjected to a reductive amination reaction in the presence of a reducing agent, such as sodium triacetoxyborohydride or sodium cyanoborohydride, and an aminocyclohexyl acetalaldehyde compound which is then subjected to a reaction deprotecting the amine function, for example in the presence of trifluoroacetic acid, to yield the desired compound.

公开(公告)号：PE01562011A1

公开(公告)日：2011-03-19

申请号：PE0004402010

申请日：2010-07-06

Applicant: SERVIER LAB

Inventor： DE NANTEUIL GUILLAUME ,  DEKEYNE ANNE ,  CIMETIERE BERNARD ,  MILLAN MARK

IPC: A61K31/407 ,  A61P25/00 ,  A61P25/16 ,  A61P25/18 ,  C07D491/052

CPC classification number: C07D491/04

Abstract: SE REFIERE A UN COMPUESTO DERIVADO CROMENICO DE FORMULA (I) DONDE R1 Y R2 FORMAN LA CADENA CARBONADA 1-ETILPROPANAMINA DISUSTITUIDA EN N POR R3 Y R4; R3 ES H, ALQUILO C1-C6 LINEAL O RAMIFICADO; R4 ES H, ALQUILO C1-C6 LINEAL O RAMIFICADO, ARILO, ENTRE OTROS. SON COMPUESTOS PREFERIDOS (3aS,9bR)-2-[2-(trans-4-AMINOCICLOHEXIL)ETIL]-1,2,3,3a,4,9b-HEXAHIDROCROMENO[3,4-c]PIRROL-8-CARBONITRILO; (3aS,9bR)-2-{[2-(trans-4-METILAMINO)CICLOHEXIL]ETIL}-1,2,3,3a,4,9b-HEXAHIDROCROMENO[3,4-c]PIRROL-8-CARBONITRILO; N-(trans-4-{2-[(3aS,9bR)-8-CIANO-1,3a,4,9b-TETRAHIDROCROMENO[3,4-c]PIRROL-2(3H)-IL]ETIL}CICLOHEXIL)ACETAMIDA; ENTRE OTROS. SE REFIERE TAMBIEN A UN METODO DE PREPARACION Y A UNA COMPOSICION FARMACEUTICA. DICHO COMPUESTO ES UN ANTAGONISTA DE LOS RECEPTORES DOPAMINERGICOS D2 Y D3 UTIL EN EL TRATAMIENTO DE ESQUIZOFRENIA, ENFERMEDAD DE PARKINSON, DEPRESION, ENTRE OTROS

公开(公告)号：NO328014B1

公开(公告)日：2009-11-09

申请号：NO20021806

申请日：2002-04-17

Applicant: SERVIER LAB

Inventor： LAVIELLE GILBERT ,  BROCCO MAURICETTE ,  MILLAN MARK ,  DUBUFFET THIERRY ,  MULLER OLIVIER ,  DEKEYNE ANNE

IPC: C07D491/048 ,  A61K31/519 ,  A61P1/14 ,  A61P15/10 ,  A61P15/12 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07D471/00 ,  C07D471/04 ,  C07D491/052 ,  C07D513/00 ,  C07D519/00

Abstract: Compound of formula (I): wherein: R1, R2, R3 and R4, which may be the same or different, each represent a hydrogen atom, a halogen atom or a group selected from alkyl, alkoxy, polyhaloalkyl, hydroxy, cyano, nitro and amino, or R1 with R2, R2 with R3, or R3 with R4, together with the carbon atoms carrying them, form an optionally substituted benzene ring or an optionally substituted heteroaromatic ring, X represents an oxygen atom or a methylene group, A represents an alkylene chain, represents an optionally substituted, unsaturated, nitrogen-containing heterocycle and R5 represents an alkyl group, its enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid. a medicinal products containing the same are useful as a double alpha2/5-HT2c antagonist.

公开(公告)号：ES2246380T3

公开(公告)日：2006-02-16

申请号：ES02290945

申请日：2002-04-16

Applicant: SERVIER LAB

Inventor： LAVIELLE GILBERT ,  DUBUFFET THIERRY ,  MULLER OLIVIER ,  MILLAN MARK ,  DEKEYNE ANNE ,  BROCCO MAURICETTE

IPC: A61K31/519 ,  A61P1/14 ,  A61P15/10 ,  A61P15/12 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07D471/00 ,  C07D471/04 ,  C07D491/048 ,  C07D491/052 ,  C07D513/00 ,  C07D519/00 ,  C07D491/04 ,  C07D513/04 ,  A61K31/505

Abstract: Compuestos de fórmula (I): en la cual: R1, R2, R3 y R4, idénticos o diferentes, representan cada uno un átomo de hidrógeno, de halógeno o un grupo seleccionado entre alquilo(C1-C6) lineal o ramificado, alcoxi(C1-C6) lineal o ramificado, polihaloalquilo (C1-C6) lineal o ramificado, hidroxilo, ciano, nitro o amino, o bien R1 con R2, R2 con R3 o R3 con R4 forman juntos, con los átomos de carbono que los portan, un anillo bencénico eventualmente sustituido o heteroaromático eventualmente sustituido, X representa un átomo de oxígeno o un grupo metileno, A representa una cadena alquileno(C1-C6) lineal o ramificada, N B representa un heterociclo de nitrógeno insaturado, eventualmente sustituido con uno o dos sustituyentes, idénticos o diferentes, seleccionados de entre átomos de halógeno y los grupos alquilo(C1-C6) lineal o ramificado, hidroxilo, alcoxi(C1-C6) lineal o ramificado, polihaloalquilo(C1-C6) lineal o ramificado, ciano, nitro, amino, fenilo eventualmente sustituido, tienilo eventualmente sustituido, furilo eventualmente sustituido y pirrolilo eventualmente sustituido, y R5 representa un grupo alquilo(C1-C6) lineal o ramificado, sus enantiómeros, diastereoisómeros, así como sus sales de adición de un ácido o de una base farmacéuticamente aceptables.

公开(公告)号：ES2238260T3

公开(公告)日：2005-09-01

申请号：ES00402799

申请日：2000-10-11

Applicant: SERVIER LAB

Inventor： LAVIELLE GILBERT ,  MULLER OLIVIER ,  MILLAN MARK ,  CUSSAC DIDIER ,  DEKEYNE ANNE

IPC: A61K31/395 ,  A61K31/40 ,  A61K31/4045 ,  A61K31/428 ,  A61K31/437 ,  A61K31/502 ,  A61K31/505 ,  A61K31/513 ,  A61K31/517 ,  A61K31/519 ,  A61K31/53 ,  A61K31/54 ,  A61P1/08 ,  A61P25/00 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  A61P43/00 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04

Abstract: Compuestos de fórmula (I): **(Fórmula)** en la cual: ¿ R1 y R2 representan independientemente un átomo de hidrógeno o un grupo alquilo de 1 a 6 carbonos lineal o ramificado, ¿ T1 y T2 representan independientemente un grupo alquileno de 1 a 6 carbonos lineal o ramificado, ¿ G representa un grupo heterocíclico de fórmula (alfa) ó (beta): donde: W1 a W5 y X1 a X4 son seleccionados con el fin de formar un grupo químicamente estable, y se definen de la forma siguiente: - W1, W2 y W3 representan independientemente un átomo de nitrógeno, un grupo CR5, NR4 ó CO, - W4 representa un átomo de nitrógeno, un grupo CR3, NR4 ó CO, - W5 representa un átomo de carbono o un átomo de nitrógeno, - X1 representa un enlace, un átomo de nitrógeno o un grupo CR3 ó NR4, - X2 a X4 representan independientemente un grupo CR3, NR4, CO, SR4 ó SO2 o bien un átomo de oxígeno, de azufre o de nitrógeno, - R3 representa un átomo de hidrógeno, de halógeno, un grupo alquilo de 1 a 6 carbonos lineal o ramificado, hidroxilo, perhaloalquilo de 1 a 6 carbonos lineal o ramificado, nitro o amino (eventualmente sustituido con uno o dos grupos alquilo de 1 a 6 carbonos lineales o ramificados, o bencilo), - R4 representa un átomo de hidrógeno o un grupo alquilo de 1 a 6 carbonos lineal o ramificado, arilo eventualmente sustituido, arilalquilo eventualmente sustituido, - R5 representa un grupo R3 o bien dos grupos R5 adyacentes forman junto con los átomos de carbono que los llevan un grupo mono o bicíclico saturado, parcialmente insaturado o insaturado, que contiene eventualmente de 1 a 5 heteroátomos seleccionados entre nitrógeno, oxígeno y azufre, estando el citado grupo eventualmente sustituido con uno o varios grupos R3 u oxo.

公开(公告)号：DE60104776T2

公开(公告)日：2005-09-01

申请号：DE60104776

申请日：2001-06-29

Applicant: SERVIER LAB

Inventor： LAVIELLE GILBERT ,  MULLER OLIVIER ,  MILLAN MARK ,  DEKEYNE ANNE ,  BROCCO MAURICETTE

IPC: C07D295/08 ,  A61K31/4164 ,  A61K31/4168 ,  A61K31/4174 ,  A61K31/4178 ,  A61K31/4725 ,  A61K31/495 ,  A61K31/496 ,  A61K31/497 ,  A61P15/00 ,  A61P15/10 ,  A61P25/00 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  C07C275/28 ,  C07D209/08 ,  C07D233/24 ,  C07D233/50 ,  C07D233/54 ,  C07D233/64 ,  C07D233/66 ,  C07D235/10 ,  C07D235/14 ,  C07D235/30 ,  C07D295/12 ,  C07D295/135 ,  C07D319/20 ,  C07D401/04 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12

Abstract: Heterocyclic-substituted N,N'-diphenylurea derivatives (I) are new. Urea derivatives of formula (I) and their enantiomers, diastereomers and acid or base addition salts are new. R1 - R4 = H, halo, alkyl, alkoxy, OH, alkylthio, SH, CN, NH2, mono- or dialkylamino, NO2, COOH, alkoxycarbonyl, CONH2 or mono- or dialkylaminocarbonyl; or two adjacent groups together complete a fused benzene ring or a 5-7 membered heteroaryl ring containing 1-3 of N, O and/ore S as heteroatoms; L1, L2 = H or together form CH2CH2; X1 = direct bond (bonded in the 2- or 3-position of the ring); and X2 = H, halo, alkyl, alkoxy, OH, NO2, CN, NH2 or mono- or dialkylamino; or X1 + X2 = group forming a 4-7C ring with the C atoms in the 3- and 4-positions of the ring, 1 or 2 CH2 units of the ring optionally being replaced by O, NH or N(alkyl) and G being bonded to a ring C; X3 = H, halo, alkyl, alkoxy, OH, NO2, CN, NH2 or mono- or dialkylamino; G = heterocyclic group of formula (G1)-(G3); dotted line = optional bond; Alk = 1-6C alkylene, which must be bonded at the 2-position in an imidazoline ring of (G1); n, m = 0 or 1; T3, T4 = alkyl; or aryl, arylalkyl, heteroaryl or heteroarylalkyl (all optionally ring-substituted by one or more of halo, alkyl, alkoxy, OH, SH, alkylthio, CN, NH2, mono- or dialkylamino, NO2, COOH, alkoxycarbonyl, CONH2 or mono- or dialkylaminocarbonyl; heteroaryl rings may additionally be mono-substituted by oxo); aryl moieties = phenyl, naphthyl or biphenylyl; heteroaryl moieties = mono- or bicyclic group in which at least one ring is aromatic, containing 1-5 of N, O and/or S as heteroatom(s); alkyl moieties have 1-6C. Independent claims are included for the preparation of (I).

公开(公告)号：DK1092715T3

公开(公告)日：2005-07-25

申请号：DK00402799

申请日：2000-10-11

Applicant: SERVIER LAB

Inventor： LAVIELLE GILBERT ,  MULLER OLIVIER ,  MILLAN MARK ,  DEKEYNE ANNE ,  CUSSAC DIDIER

IPC: A61K31/395 ,  A61K31/40 ,  A61K31/4045 ,  A61K31/428 ,  A61K31/437 ,  A61K31/502 ,  A61K31/505 ,  A61K31/513 ,  A61K31/517 ,  A61K31/519 ,  A61K31/53 ,  A61K31/54 ,  A61P1/08 ,  A61P25/00 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  A61P43/00 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04

Abstract: Cyano indoles (I), their enantiomers, diastereoisomers, and their salts with acids and bases, their preparation, and pharmaceutical compositions containing them. Cyano indoles of formula (I): R1 and R2 = H or 1-6C alkyl; T1 and T2 = 1-6C alkylene; G = a heterocyclic group of formula (a) or (b); W1, W2 and W3 = N, CR5, NR4 or CO; W4 = N, CR3, NR4, or CO; W5 = C or N; X1 = a bond, N, CR3 or NR4; X2 to X4 = CR3, NR4, CO, SR4, SO2, O, S, or N; R3 = H, halogen, 1-6C alkyl, OH, 1-6C perhaloalkyl, NO2, NH2, mono- or di alkylamino, or benzylamino; R4 = H, 1-6C alkyl, or optionally substituted aryl or aralkyl; and R5 = a group R3 or two adjacent groups R5 form, together with the C atoms to which they are attached, a saturated or unsaturated mono- or bicyclic group that may contain 1-5 O, N, or S hetero atoms and which may be substituted by R3 or oxo.

公开(公告)号：DK1170288T3

公开(公告)日：2004-11-29

申请号：DK01401712

申请日：2001-06-29

Applicant: SERVIER LAB

Inventor： MILLAN MARK ,  LAVIELLE GILBERT ,  MULLER OLIVIER ,  DEKEYNE ANNE ,  BROCCO MAURICETTE

IPC: C07D295/08 ,  A61K31/4164 ,  A61K31/4168 ,  A61K31/4174 ,  A61K31/4178 ,  A61K31/4725 ,  A61K31/495 ,  A61K31/496 ,  A61K31/497 ,  A61P15/00 ,  A61P15/10 ,  A61P25/00 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  C07C275/28 ,  C07D209/08 ,  C07D233/24 ,  C07D233/50 ,  C07D233/54 ,  C07D233/64 ,  C07D233/66 ,  C07D235/10 ,  C07D235/14 ,  C07D235/30 ,  C07D295/12 ,  C07D295/135 ,  C07D319/20 ,  C07D401/04 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12

Abstract: Heterocyclic-substituted N,N'-diphenylurea derivatives (I) are new. Urea derivatives of formula (I) and their enantiomers, diastereomers and acid or base addition salts are new. R1 - R4 = H, halo, alkyl, alkoxy, OH, alkylthio, SH, CN, NH2, mono- or dialkylamino, NO2, COOH, alkoxycarbonyl, CONH2 or mono- or dialkylaminocarbonyl; or two adjacent groups together complete a fused benzene ring or a 5-7 membered heteroaryl ring containing 1-3 of N, O and/ore S as heteroatoms; L1, L2 = H or together form CH2CH2; X1 = direct bond (bonded in the 2- or 3-position of the ring); and X2 = H, halo, alkyl, alkoxy, OH, NO2, CN, NH2 or mono- or dialkylamino; or X1 + X2 = group forming a 4-7C ring with the C atoms in the 3- and 4-positions of the ring, 1 or 2 CH2 units of the ring optionally being replaced by O, NH or N(alkyl) and G being bonded to a ring C; X3 = H, halo, alkyl, alkoxy, OH, NO2, CN, NH2 or mono- or dialkylamino; G = heterocyclic group of formula (G1)-(G3); dotted line = optional bond; Alk = 1-6C alkylene, which must be bonded at the 2-position in an imidazoline ring of (G1); n, m = 0 or 1; T3, T4 = alkyl; or aryl, arylalkyl, heteroaryl or heteroarylalkyl (all optionally ring-substituted by one or more of halo, alkyl, alkoxy, OH, SH, alkylthio, CN, NH2, mono- or dialkylamino, NO2, COOH, alkoxycarbonyl, CONH2 or mono- or dialkylaminocarbonyl; heteroaryl rings may additionally be mono-substituted by oxo); aryl moieties = phenyl, naphthyl or biphenylyl; heteroaryl moieties = mono- or bicyclic group in which at least one ring is aromatic, containing 1-5 of N, O and/or S as heteroatom(s); alkyl moieties have 1-6C. Independent claims are included for the preparation of (I).