公开(公告)号：NO322569B1

公开(公告)日：2006-10-30

申请号：NO20022285

申请日：2002-05-14

Applicant: SERVIER LAB

Inventor： BOULANGER MICHELLE ,  NANTEUIL GUILLAUME DE ,  PORTEVIN BERNARD ,  LEVENS NIGEL ,  BENOIST ALAIN ,  NOSJEAN OLIVIER ,  HUSSON-ROBERT BERNADETTE

IPC: C07D295/10 ,  A61K31/40 ,  A61K31/426 ,  A61P3/04 ,  A61P3/08 ,  A61P3/10 ,  C07D207/16 ,  C07D277/04 ,  C07D277/06 ,  C07D295/185 ,  C07K5/02

Abstract: Alpha amino acid derivatives (I), their optical isomers and addition salts, are new. Alpha amino acid derivatives of formula (I), their optical isomers and addition salts, are new: A = five-membered heterocycle, optionally substituted by a cyano group; Ak = 1-6C alkylene; X = single bond or phenylene; R1, R2, R4 = H or 1-6C alkyl; Y = NR4 or CH-NO2; R3 = NO2 or CN; and provided that: (i) when Y is CH-NO2, then R3 may further be 1-6C alkyl; and (ii) when A is unsubstituted, then Ak is propylene, X is a bond, Y is NH and R3 is NO2, are excluded.

公开(公告)号：AU2005201198A1

公开(公告)日：2005-10-06

申请号：AU2005201198

申请日：2005-03-18

Applicant: SERVIER LAB

Inventor： RUPIN ALAIN ,  PAMENTIER JEAN-GILES ,  VERBEUREN TONY ,  GLOANEC PHILLIPPE ,  BENOIST ALAIN ,  VALLEZ MARIE-ODILE ,  NANTEUIL GUILLAUME DE

IPC: A61K31/519 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P43/00 ,  C07D487/04 ,  A61K31/4196 ,  A61K31/381 ,  A61K31/395 ,  A61K31/00

Abstract: 4-Oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrazine-6-carboxamide compounds (I) are new. 4-Oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrazine-6-carboxamide compounds of formula (I) are new. A : 1-oxidopyridyl substituted by the remainder of the molecule in any one of the positions 2, 3 and 4; m, n : 1 - 3; R 1H or linear or branched (1-6C)alkyl; R 2, R 3hydrogen, halogen, linear or branched (1-6C)alkyl, hydroxy, linear or branched (1-6C)acyloxy or linear or branched (1-6C)alkoxy; R 2+R 33-6C cycloalkane; R 4, R 5H; R 4+R 5benzo ring; Ar : phenyl, biphenylyl or naphthyl (optionally substituted by at least one of T 1) or 5 - 12-membered mono- or bi-cyclic aromatic group (containing 1 - 3 heteroatoms selected from O, N or S; and optionally substituted by at least one of T 1); and T 1halo, linear or branched (1-6C)alkyl (optionally substituted by hydroxy, carboxy or carbamoyl (optionally mono- or di-substituted by linear or branched (1-6C)alkyl, linear or branched (1-6C)alkoxy, hydroxy, trihalo-(1-6C)alkyl (in which the alkyl moiety is linear or branched), amino (optionally mono- or di-substituted by linear or branched (1-6C)alkyl, carboxymethoxy or carbamoylmethoxy (optionally mono- or di-N-substituted by linear or branched (1-6C)alkyl, hydroxy-(1-6C)alkyl (in which the alkyl moiety is linear or branched), alkoxyalkyl (in which the alkoxy and alkyl moieties are each linear or branched 1-6C) or pyridylalkyl (in which the alkyl moiety is linear or branched 1-6C)))). The configuration of the asymmetric centre at the alpha position with respect to the amide is (S). [Image] ACTIVITY : Antianginal; Thrombolytic; Cardiant; Vasotropic; Cardiovascular-Gen.; Antiarteriosclerotic. MECHANISM OF ACTION : Thrombin inhibitors. The inhibitory activity of 3-{[2,2-difluoro-2-(1-oxido-2-pyridyl)ethyl]amino}-4-oxo-N-[2-(2-oxo-2-{[2-(2-pyridyl)ethyl]amino}ethoxy)benzyl]-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrazine-6-carboxamide hydrochloride (A) was evaluated on human thrombin. The purified human fibrinogen (4 mM) was added to thrombin (0.7 nM) that had previously been incubated optionally with the inhibitor to be tested (20[deg]C, 10 minutes). Inhibitors, enzymes and substrates were diluted in the same buffer (0.01 mM phosphate buffer, pH 7.4, containing sodium chloride (0.12 M) and bovine serum albumin (0.05%)) and then distributed on a polystyrene microtitre plate in a volume of 50 mu l. The fibrin formed by the thrombin was measured using a spectrophotometer at 405 nm after 10 - 15 minutes reaction at 20[deg]C. The IC 50 value of (A) was found to be 1.4 nM.

公开(公告)号：NO20051367A

公开(公告)日：2005-09-20

申请号：NO20051367

申请日：2005-03-16

Applicant: SERVIER LAB

Inventor： NANTEUIL GUILLAUME DE ,  VERBEUREN TONY ,  VALLEZ MARIE-ODILE ,  RUPIN ALAIN ,  BENOIST ALAIN ,  PARMENTIER JEAN-GILLES ,  GLOANEC PHILIPPE

IPC: A61K31/519 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P43/00 ,  C07D487/04 ,  A61K31/498

CPC classification number: C07D487/04

公开(公告)号：CA2500575A1

公开(公告)日：2005-09-19

申请号：CA2500575

申请日：2005-03-14

Applicant: SERVIER LAB

Inventor： GLOANEC PHILIPPE ,  VALLEZ MARIE-ODILE ,  BENOIST ALAIN ,  DE NANTEUIL GUILLAUME ,  PARMENTIER JEAN-GILLES ,  VERBEUREN TONY ,  RUPIN ALAIN

IPC: A61K31/519 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P43/00 ,  C07D487/04 ,  C07B31/00 ,  A61K31/4985

Abstract: Composé de formule (I) dans laquelle * représente un groupement 1-oxydo-pyridinyle substit ué par le reste de la molécule en l'une quelconque des positions 2, 3 ou 4, * m et n, identiques ou différents, représentent chacun un entier compris entre 1 et 3, * R, représente un atome d'hydrogène ou un groupement alkyle, * R2 et R3, identiques ou différents, représentent chacun un atome ou groupement choisi parmi les atomes d'hydrogène et d'halogène et les groupements alkyle, hydrox y, acyloxy et alkoxy, ou forment ensemble, avec l'atome de carbone qui les port e, un cycloalcane ayant de 3 à 6 atomes de carbone, * R4 et R5 représentent chacun un atome d'hydrogène, ou sont adjacents et forment ensemble, avec les atomes de carbone gui les portent, un cycle benzo, * Ar représente un groupement aryle ou hétéroaryle. Médicaments.

公开(公告)号：FR2824825B1

公开(公告)日：2005-05-06

申请号：FR0106375

申请日：2001-05-15

Applicant: SERVIER LAB

Inventor： DE NANTEUIL GUILLAUME ,  PORTEVIN BERNARD ,  BENOIST ALAIN ,  LEVENS NIGEL ,  NOSJEAN OLIVIER ,  HUSSON ROBERT BERNADETTE ,  BOULANGER MICHELLE

IPC: C07D295/10 ,  A61K31/40 ,  A61K31/426 ,  A61P3/04 ,  A61P3/08 ,  A61P3/10 ,  C07D207/16 ,  C07D277/04 ,  C07D277/06 ,  C07D295/185 ,  C07K5/02 ,  C07D207/42

Abstract: Alpha amino acid derivatives (I), their optical isomers and addition salts, are new. Alpha amino acid derivatives of formula (I), their optical isomers and addition salts, are new: A = five-membered heterocycle, optionally substituted by a cyano group; Ak = 1-6C alkylene; X = single bond or phenylene; R1, R2, R4 = H or 1-6C alkyl; Y = NR4 or CH-NO2; R3 = NO2 or CN; and provided that: (i) when Y is CH-NO2, then R3 may further be 1-6C alkyl; and (ii) when A is unsubstituted, then Ak is propylene, X is a bond, Y is NH and R3 is NO2, are excluded.

公开(公告)号：SI1217002T1

公开(公告)日：2004-12-31

申请号：SI200130194

申请日：2001-12-21

Applicant: SERVIER LAB

Inventor： DE NANTEUIL GUILLAUME ,  BENOIST ALAIN ,  PASTOUREAU PHILIPPE ,  SABATINI MASSIMO ,  HICKMAN JOHN ,  PIERRE ALAIN ,  TUCKER GORDON

IPC: C07D491/048 ,  A61K31/4433 ,  A61K31/444 ,  A61K31/541 ,  A61P9/10 ,  A61P19/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07D405/14 ,  C07D417/14 ,  C07D491/04

Abstract: 5-Sulfonyl-2-(4-pyridinyl)-benzofuran, benzothiophene or indole derivatives (I), containing a hydroxamic acid function, are new. Benzofuran, benzothiophene or indole derivatives of formula (I) and their isomers, N-oxides and acid or base addition salts are new. R1 = H, halo, 1-6C alkyl or 1-6C alkoxy; X = O, S or NR; R = H or 1-6C alkyl; A = N-hydroxy-carboxamido-substituted tetrahydrofuropyridine, thiomorpholine or tetrahydropyranylmethyl group of formula (i)-(iii); Ra = H, halo, 1-6C alkyl or 1-6C alkoxy; Rb, Rc = H or 1-6C alkyl; and n = 0-2. An Independent claim is also included for the preparation of (I).

公开(公告)号：AR035409A1

公开(公告)日：2004-05-26

申请号：ARP010105928

申请日：2001-12-20

Applicant: SERVIER LAB

Inventor： TUCKER GORDON ,  DE NANTEUIL GUILLAUME ,  BENOIST ALAIN ,  PASTOUREAU PHILIPPE ,  SABATINI MASSIMO ,  HICKMAN JOHN ,  PIERRE ALAIN

IPC: C07D491/048 ,  A61K31/4433 ,  A61K31/444 ,  A61K31/541 ,  A61P9/10 ,  A61P19/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07D405/14 ,  C07D417/14 ,  C07D491/04

Abstract: Compuestos inhibidores de metalo proteasas de fórmula (1): en la cual R1 representa un átomo de halógeno, un grupo alquilo (C1-6) lineal o ramificado o un grupo alcoxi (C1-6) lineal o ramificado, X representa un átomo de oxígeno, un átomo de azufre o un grupo NR en el cual R representa un átomo de hidrógeno o un grupo alquilo (C1-6) lineal o ramificado, A representa cualquiera de los grupos (2), en el cual Ra representa un átomo de hidrógeno, un átomo de halógeno, un grupo alquilo (C1-6) lineal o ramificado; (3) en el cual Rb, Rc son idénticos o diferentes, representa un átomo de hidrógeno o un grupo alquilo (C1-6) lineal o ramificado, y n es 0, 1 o 2; o (4), sus isómeros, N-óxidos y sus sales de adición con un ácido o con una base farmacéuticamente aceptable. Estos compuestos han demostrado ser más poderosos que aquellos descriptos en la literatura, que los hace por lo tanto potencialmente útiles para el tratamiento de los cánceres de las enfermedades reumáticas, como la artrosis y la artritis reumatoide, de la arteriosclerosis etc. Su procedimiento de preparación y las composiciones farmacéuticas que los contienen.

公开(公告)号：ES2198262T3

公开(公告)日：2004-02-01

申请号：ES00401864

申请日：2000-06-30

Applicant: SERVIER LAB

Inventor： DE NANTEUIL GUILLAUME ,  BENOIST ALAIN ,  BONNET JACQUELINE ,  SABATINI MASSIMO ,  ATASSI GHANEM ,  PIERRE ALAIN

IPC: C07D307/77 ,  A61K31/4355 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4453 ,  A61K31/506 ,  A61K31/5377 ,  A61P9/10 ,  A61P19/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07D491/04 ,  C07D491/048

Abstract: N-Arylsulfonyl tetrahydrofuropyridine carboxylic acid derivatives (I), their isomers and acid and base addition salts, their preparation and compositions containing them. N-Arylsulfonyl tetrahydrofuropyridine carboxylic acid derivatives of formula (I), their isomers and acid and base addition salts, their preparation and compositions containing them: R1 = H, halogen, 1-6C alkyl or alkoxy; R2 = OH, 1-6C alkoxy, or NHOH; Ar1 = phenylene or biphenylene; X = O, S, NR, -OC- or a bond; R = H, or 1-6C alkyl; n = 0-6; Ar2 = phenyl substituted by heteroaryl, biphenyl substituted by heteroaryl, pyridinyl substituted by heteroaryl, or a heterocycle

公开(公告)号：AR033735A1

公开(公告)日：2004-01-07

申请号：ARP020101750

申请日：2002-05-14

Applicant: SERVIER LAB

Inventor： DE NANTEUIL GUILLAUME ,  PORTEVIN BERNARD ,  BENOIST ALAIN ,  LEVENS NIGEL ,  NOSJEAN OLIVIER ,  HUSSON-ROBERT BERNADETTE ,  BOULANGER MICHELLE

IPC: C07D295/10 ,  A61K31/40 ,  A61K31/426 ,  A61P3/04 ,  A61P3/08 ,  A61P3/10 ,  C07D207/16 ,  C07D277/04 ,  C07D277/06 ,  C07D295/185 ,  C07K5/02 ,  C07D295/18 ,  A61K31/33

Abstract: Compuesto de fórmula (1), en la cual fórmula (2) representa un heterociclo que contiene nitrógeno de 5 miembros; Ak representa una cadena alquileno; X representa un enlace simple o un grupo fenileno; R1 y R2, que pueden ser idénticos o diferentes, cada uno representa un átomo de hidrógeno o un grupo alquilo; R3 representa un grupo alquilo, nitro o ciano, cuando Y es CH-NO2; o nitro y ciano cuando Y representa NR4; Y representa NR4 o CH-NO2; R4 representa un átomo de hidrógeno o un grupo alquilo; sus tautómeros cuando estos existen, sus isómeros ópticos y sales de adición de los mismos con un ácido farmacéuticamente aceptable, con exclusión de los compuestos en los cuales, simultáneamente, fórmula (2) representa un heterociclo que contiene nitrógeno de 5 miembros no sustituido; Ak representa el grupo -(CH2)3-; X representa un enlace simple; Y representa NH y R3 representa el grupo nitro. Medicamentos para la intolerancia de glucosa y trastornos asociados a hiperglucemia.

公开(公告)号：NZ518948A

公开(公告)日：2003-10-31

申请号：NZ51894802

申请日：2002-05-14

Applicant: SERVIER LAB

Inventor： DE NANTEUIL GUILLAUME ,  PORTEVIN BERNARD ,  BENOIST ALAIN ,  LEVENS NIGEL ,  NOSJEAN OLIVIER ,  HUSSON-ROBERT BERNADETTE ,  BOULANGER MICHELLE

IPC: A61K31/40 ,  A61K31/426 ,  A61P3/04 ,  A61P3/08 ,  A61P3/10 ,  C07D207/16 ,  C07D295/10 ,  C07D277/04 ,  C07D277/06 ,  C07D295/185 ,  C07K5/02 ,  C07D207/06 ,  A61K31/425

Abstract: A compound of formula (I) wherein; NA represents a 5-membered nitrogen containing heterocycle optionally substituted by a cyano group; Ak represents an alkylene chain; X represents a single bond or a phenylene group; R1 and R2 each represent H or alkyl; Y represents NR4 or CH-NO2, where R4 is H or alkyl; R3 represents alkyl, nitro or cyano when Y represents CH-NO2 or cyano or nitro when Y is NR4. Also described are pharmaceutical compositions containing formula (I) and a process for making it.