公开(公告)号：FR2865474B1

公开(公告)日：2008-06-13

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

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.

公开(公告)号：EA009698B1

公开(公告)日：2008-02-28

申请号：EA200500072

申请日：2005-01-24

Applicant: SERVIER LAB

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

IPC: C07D285/24 ,  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

Abstract: Настоящееизобретениеотноситсяк соединениямформулы (I)вкоторой Rпредставляетсобойлинейнуюилиразветвленнуюмонофтор- илиполифтор-С-Салкильнуюгруппу, Rпредставляетсобойатомводородаилигруппу, выбраннуюизлинейногоилиразветвленногоС-Салкилаи излинейногоилиразветвленного C-Салкиламинокарбонила, Rпредставляетсобойатомводорода, R, R, Rи R, которыемогутбытьодинаковымиилиразными, каждыйпредставляетсобойатомилигруппу, выбранный(ую) изатомовводородаи галогенаи нитрогруппы, линейногоилиразветвленного C-Салкилсульфонила, линейногоилиразветвленногоС-Салкоксии линейногоилиразветвленного C-Салкила, необязательнозамещенногооднимилинесколькимиатомамигалогена, атакжек ихсолямприсоединенияс фармацевтическиприемлемойкислотойилиоснованием. Такжеописаныпромежуточныесоединенияформулы (VI)способыполучениясоединенийформулы (I), содержащиеихфармацевтическиекомпозициии ихприменениев качествеположительныхаллостерическихмодуляторовАМРАрецепторов.

公开(公告)号：CA2492161A1

公开(公告)日：2005-07-26

申请号：CA2492161

申请日：2005-01-10

Applicant: SERVIER LAB

Inventor： LESTAGE PIERRE ,  DANOBER LAURENCE ,  PIROTTE BERNARD ,  DE TULLIO PASCAL ,  FRAIKIN PIERRE ,  CAIGNARD DANIEL-HENRI ,  FRANCOTTE PIERRE ,  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 ,  A61K31/54

Abstract: Composé de formule (I): (voir formule I) dans laquelle : ~ R F représente un groupement mono- ou poly- fluoroalkyle, ou monofluoro- o u polyfluoro- cycloalkylalkyle, ~ R1 représente un atome d'hydrogène ou un groupement choisi parmi alkylaminocarbonyle et alkyle éventuellement substitué, ~ R2 représente un atome d'hydrogène ou d'halogène ou un groupement choisi parmi cycloalkyle et alkyle éventuellement substitué, ~ R3 à R6, identiques ou différents, représentent chacun un atome ou un groupement choisi parmi les atomes d'hydrogène, d'halogène et les groupements nitro, cyano, alkylsulfonyle, hydroxy, alkoxy, alkyle éventuellement substitué, et amino éventuellement substitué, ainsi que leurs sels d'addition avec un acide ou une base pharmaceutiquement acceptable, et leurs isomères optiques lorsqu'ils existent. Médicaments.

公开(公告)号：GEP20063960B

公开(公告)日：2006-11-10

申请号：GEAU2005008596

申请日：2005-01-24

Applicant: SERVIER LAB

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

IPC: C07D285/24 ,  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

Abstract: A compound of the formula wherein R1 – R6 and Rf are defined in the description and pharmaceutical composition containing them. Said compounds are useful for treatment of disorders of memory and cognition, Alzheimer's disease, Parkinson's diseases and other progressive neurodegenerative diseases.

公开(公告)号：ZA200500774B

公开(公告)日：2005-08-10

申请号：ZA200500774

申请日：2005-01-26

Applicant: SERVIER LAB

Inventor： FRANCOTTE PIERRE ,  FRAIKIN PIERRE ,  TULLIO PASCAL DE ,  PIROTTE BERNARD ,  LESTAGE PIERRE ,  DANOBER LAURENCE ,  CAIGNARD DANEIL-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 ,  C07D ,  A61K ,  A61P

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.

公开(公告)号：UA86574C2

公开(公告)日：2009-05-12

申请号：UAA200500666

申请日：2005-01-25

Applicant: SERVIER LAB

Inventor： FRANCOTTE PIERRE ,  FRAIKIN PIERRE ,  TULLIO PASCAL DE ,  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

Abstract: Соединенияформулы (І):, (І)где:Rпредставляетсобоймонофтор- илиполифторалкильнуюилимонофтор- илиполифторциклоалкилалкильнуюгруппу,Rпредставляетсобойатомводородаилигруппу, выбраннуюизалкиламинокарбонилаилинеобязательнозамещенногоалкила,Rпредставляетсобойатомводородаилигалогенаилигруппу, выбраннуюизциклоалкилаилинеобязательнозамещенногоалкила,от Rдо R, которыемогутбытьодинаковымиилиотличаться, каждыйпредставляетсобойатомилигруппу, выбраннуюизатомовводородаи галогенаи группнитро, циано, алкилсульфонила, гидрокси, алкокси, необязательнозамещенногоалкила,атакжеихаддитивныесолис фармацевтическиприемлемойкислотойилиосновой, иихоптическиеизомеры, когдаонисуществуют.

公开(公告)号：HK1079778A1

公开(公告)日：2006-04-13

申请号：HK05111844

申请日：2005-12-22

Applicant: SERVIER LAB

Inventor： FRANCOTTE PIERRE ,  FRAIKIN PIERRE ,  PIROTTE PASCAL ,  LESTAGE PIERRE ,  DANOBER LAURENCE ,  CAIGNARD DANIEL-HENRI ,  RENARD PIERRE

IPC: C07D20060101 ,  A61K20060101 ,  A61K31/5415 ,  A61K31/549 ,  A61P20060101 ,  A61P9/10 ,  A61P25/00 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07B53/00 ,  C07D285/22 ,  C07D285/24

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.

公开(公告)号：NO20050391A

公开(公告)日：2005-07-27

申请号：NO20050391

申请日：2005-01-25

Applicant: SERVIER LAB

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

IPC: C07D285/24 ,  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

CPC classification number: C07D285/24

公开(公告)号：AR047455A1

公开(公告)日：2006-01-18

申请号：ARP050100244

申请日：2005-01-25

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: Reivindicacion 1: Compuestos de formula (1), en la cual: RF representa un grupo monofluoro- o polifluoro-alquilo(C1-6) lineal o ramificado o un grupo monofluoro- o polifluoro-cicloalquilalquilo, donde la parte alquilo es C1-6 y lineal o ramificado, y la parte cicloalquilo es C3-7; R1 representa un átomo de hidrogeno o un grupo seleccionado entre alquilo C1-6 lineal o ramificado opcionalmente sustituido por uno o más átomos de halogeno, preferentemente fluor, y alquilaminocarbonilo C1-6 lineal o ramificado; R2 representa un átomo de hidrogeno o de halogeno o un grupo seleccionado entre alquilo C1-6 lineal o ramificado opcionalmente sustituido por uno o más átomos de halogeno, y cicloalquilo C3-7; R3, R4, R5 y R6, que pueden ser iguales o diferentes, representan, cada uno de ellos, un átomo o grupo seleccionado entre los átomos de hidrogeno y de halogeno y los grupos nitro, ciano, alquilsulfonilo C1-6 lineal o ramificado, hidroxi, alcoxi C1-5 lineal o ramificado, alquilo C1-6 lineal o ramificado opcionalmente sustituido por uno o más átomos de halogeno, y amino opcionalmente sustituido por uno o dos grupos alquilo lineal o ramificado; y también sus sales de adicion con un ácido o una base farmacéuticamente aceptable, y sus isomeros opticos cuando éstos están presentes, entendiéndose que R3 representa un átomo de hidrogeno cuando R6 no representa un átomo de hidrogeno.

公开(公告)号：NZ537877A

公开(公告)日：2005-10-28

申请号：NZ53787705

申请日：2005-01-25

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 ,  C07D285/18 ,  A61P25/18 ,  A61K31/5513

Abstract: Compounds of formula (I) are disclosed. Also disclosed is a process for their preparation. Compounds of formula (I) are useful in the manufacture of medicaments for use as AMPA modulators. The described compounds are also useful in the manufacture of a medicament for use in the treatment or prevention of disorders of memory and cognition that are associated with: -age -syndromes of anxiety or depression -progressive neurodegenerative diseases -Alzheimer's disease -Parkinson's disease -Pick's disease -Huntington's chorea -Korsakoff's disease -schizophrenia -sequelae of acute neurodegenerative diseases -frontal lobe and subcortical dementias -the sequelae of ischaemia -the sequelae of epilepsy.