公开(公告)号：JP2001270865A

公开(公告)日：2001-10-02

申请号：JP2001082991

申请日：2001-03-22

Applicant: HOFFMANN LA ROCHE

Inventor： CRAMERI YVO ,  SCALONE MICHELANGELO ,  WALDMEIER PIUS ,  WIDMER ULRICH

IPC: A61K31/445 ,  A61P25/04 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07B53/00 ,  C07B61/00 ,  C07C315/04 ,  C07C317/22 ,  C07D211/42 ,  C07D211/74

Abstract: PROBLEM TO BE SOLVED: To provide a method for selectivity producing an ethanesulfonylpiperidine derivative enantio-selectivity in a high yield without passing through an unstable intermediate. SOLUTION: This method for producing the ethanesulfonylpiperidine derivative having a stereo specific structure comprises reacting a protected amino acid ester with a 4-substituted butyric acid derivative in the presence of a base, then cyclizing, bezylating the obtained protected 3-oxopiperidine carboxylic acid alkyl salt, then decarboxylating in the presence of a strong acid, asymmetrically hydrogenating in the presence of a ruthenium complex containing a chiral disphosphine ligand and a chiral diamine, de-protecting the protection group (the order of the asymmetric hydrogenation and the de-protection can be reversed) and then reacting the de-protected product with a sulfone derivative.

公开(公告)号：ES2225330T3

公开(公告)日：2005-03-16

申请号：ES01105498

申请日：2001-03-15

Applicant: HOFFMANN LA ROCHE

Inventor： CRAMERI YVO ,  SCALONE MICHELANGELO ,  WALDMEIER PIUS ,  WIDMER ULRICH

IPC: A61K31/445 ,  A61P25/04 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07B53/00 ,  C07B61/00 ,  C07C315/04 ,  C07C317/22 ,  C07D211/42 ,  C07D211/74

Abstract: Un método para la preparación de compuestos de las **fórmulas** caracterizado porque R1-R4 son independientemente uno del otro, hidrógeno, halógeno hidroxi, amino, nitro, sulfonilamido alquilo C1-5, o acetamido; R5-R8 son independientemente uno del otro, hidrógeno, alquilo C1-5, halógeno, trifluorometilo o alcoxi C1- 5; y sus sales de adición ácidas farmacéuticamente aceptables; cuyo proceso comprende a) hacer reaccionar un éster de ácido amino protegido (1) con un derivado de ácido butírico 4 sustituido (2) en donde R9 es un grupo amino protector, preferiblemente bencilo; R10 y R10¿ son independientemente un grupo protector de ácido carboxílico; y Y representa un grupo de partida; en presencia de una base; b) ciclizar el derivado de ácido butírico alcoxicarbonilmetil amino protegido c) bencilar la sal de carboxilato alquil 3-oxo- piperidina protegida en donde AZ significa un ácido mineral o un ácido orgánico fuerte; d) descarboxilar el carboxilato del alquil 3-oxo- piperidina benciladoprotegido.

公开(公告)号：CA2341010A1

公开(公告)日：2001-09-22

申请号：CA2341010

申请日：2001-03-19

Applicant: HOFFMANN LA ROCHE

Inventor： CRAMERI YVO ,  WIDMER ULRICH ,  SCALONE MICHELANGELO ,  WALDMEIER PIUS

IPC: A61K31/445 ,  A61P25/04 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07B53/00 ,  C07B61/00 ,  C07C315/04 ,  C07C317/22 ,  C07D211/42 ,  C07D211/74

Abstract: The present invention relates to a new process for the preparation of compounds of the general formulae (see formula I-a, I-b) wherein R1-R4 are, independently from each other, hydrogen, halogen, hydroxy, amino, nitro, lower-alkyl-sulfonylamido, or acetamido; R5-R8 are, independently from each other hydrogen, lower-alkyl, halogen , trifluoromethyl or lower-alkoxy; and their pharmaceutically acceptable acid addition salts. The compounds of formulae I-a and I-b are NMDA (N-methyl-D-aspartate)- receptor-subtype selective blockers, which have a key function in modulating neuronal activity and plasticity which makes them key players in mediating processes underlying development of CNS including learning and memory formation and function.

公开(公告)号：CZ288594B6

公开(公告)日：2001-07-11

申请号：CZ66395

申请日：1995-03-15

Applicant: HOFFMANN LA ROCHE

Inventor： GODEL THIERRY ,  HUNKELER WALTER ,  STADLER HEINZ ,  WIDMER ULRICH

IPC: A61K31/41 ,  A61K31/55 ,  A61K31/5517 ,  A61P21/02 ,  A61P25/08 ,  A61P25/20 ,  A61P43/00 ,  C07D487/02 ,  C07D487/04 ,  C07D495/12 ,  C07D495/14 ,  C07D498/14

Abstract: In the present invention there are disclosed imidazodiazepines of the general formula I, in which A together with both carbon atoms designated with {alpha} and {beta} represent some of the radicals of the general formulae Ae1, Ae2 or Ae3, Q represents some of the radicals of the general formulae Qe1, Qe2 or Qe3, Re1 and Re2 represents each hydrogen, alkyl group containing 1 to 7 carbon atoms, alkenyl group containing 1 to 7 carbon atoms, alkynyl group containing 1 to 7 carbon atoms, hydroxyalkyl group containing 1 to 7 carbon atoms, alkoxyalkyl group containing 1 to 7 carbon atoms in both alkoxy and alkyl moieties, cycloalkyl group containing 3 to 6 carbon atoms, cycloalkylalkyl group containing 3 to 6 carbon atoms in the cycloalkyl moiety and 1 to 7 carbon atoms in the alkyl moiety, aminoalkyl group containing 1 to 7 carbon atoms in the alkyl moiety, alkylaminoalkyl group containing 1 to 7 carbon atoms in both the alkyl moieties, dialkylaminoalkyl group containing 1 to 7 carbon atoms

公开(公告)号：BG62210B1

公开(公告)日：1999-05-31

申请号：BG9950595

申请日：1995-03-16

Applicant: HOFFMANN LA ROCHE

Inventor： GODEL THIERRY ,  HUNKELER WALTER ,  STADLER HEINZ ,  WIDMER ULRICH

IPC: A61K31/41 ,  A61K31/55 ,  A61K31/5517 ,  A61P21/02 ,  A61P25/08 ,  A61P25/20 ,  A61P43/00 ,  C07D487/02 ,  C07D487/04 ,  C07D495/12 ,  C07D495/14 ,  C07D498/14

Abstract: The imidazodiazepines have the general formulawhere A together with the carbon atoms marked by annd mean some ofthe ressiduesQ is one of the radicalsR1 and R2 means hydrogen, lower alkyl, lower alkenyl, loweralkynyl, lower hydroxyalkyl, lower alkoxy-lower alkyl,(C3-C6)-cycloalkyl, (C3-C6)-cycloalkyl-lower alkyl, amino-loweralkyl, lower alkylamino-lower alkyl, di-lower alkylamino-loweralkyl or aryl-lower alkyl or together with the nitrogen atomforming 5- to 8-member heterocyle, optionally containing anotherheteroatom or condensed benzole ring; R3 is hydrogen and R4 islower alkyl or R3 & R4 together mean di- or trimethylene group; R5& R6 mean hydrogen, halogen, trifluoromethyl, lower alkoxy ornitro, where the - marked carbon atom has S-configuration when R3is different from H, with strongly expressed anxylolithic,anticonvulsive, muscle-relaxing and sedative-hypnotic properties.The imidazodiazepines form very good water-soluble acidic-additivesalts and for this reason they are suitable for the production ofaqeous inoculaation solutions.33 claims

公开(公告)号：BG61057B2

公开(公告)日：1996-09-30

申请号：BG9846494

申请日：1994-02-14

Applicant: HOFFMANN LA ROCHE

Inventor： SCHERSCHLICHT RICHARD R ,  WIDMER ULRICH

IPC: A61K31/47 ,  A61K31/4025 ,  A61K31/435 ,  A61K31/4375 ,  A61P25/20 ,  C07D207/12 ,  C07D401/14 ,  C07D455/04 ,  C07D455/06 ,  C07D471/04 ,  C07D213/63

Abstract: The compound (S)-1-[(10-chloro-6,7-dihydro-4-oxo-3-phenyl-4H-benzo[a]quino-lizin-1-yl)carbonyl]-3-ethoxypyrrolidine of the formula I which has valuable pharmacological properties, is described. In particular, the compound of formula I has a non-sedating, hypnotic, that is, sleep-promoting, activity and can accordingly be used for the treatment of sleep disorders.

公开(公告)号：BR9501104A

公开(公告)日：1996-04-23

申请号：BR9501104

申请日：1995-03-16

Applicant: HOFFMANN LA ROCHE

Inventor： GODEL THIERRY ,  HUNKELER WALTER ,  STADLER HEINZ ,  WIDMER ULRICH

IPC: A61K20060101 ,  A61K31/41 ,  A61K31/55 ,  C07D20060101 ,  C07D487/04 ,  C07D487/12 ,  C07D491/12 ,  C07D495/12 ,  C07D495/14

公开(公告)号：CZ66395A3

公开(公告)日：1995-10-18

申请号：CZ66395

申请日：1995-03-15

Applicant: HOFFMANN LA ROCHE

Inventor： GODEL THIERRY ,  HUNKELER WALTER ,  STADLER HEINZ ,  WIDMER ULRICH

IPC: A61K31/41 ,  A61K31/55 ,  A61K31/5517 ,  A61P21/02 ,  A61P25/08 ,  A61P25/20 ,  A61P43/00 ,  C07D487/02 ,  C07D487/04 ,  C07D495/12 ,  C07D495/14 ,  C07D498/14

Abstract: Aminomethyl-substd. oxadiazolyl-imidazodiazepines of formula (I) and their addn salts are new: A and C atoms alpha and beta form a gp of formula e.g. (A ):Q = a gp. of formula e.g. (Q ):R , R = H; lower alkyl,etc.;or NR R = 5-8 membered heterocycle opt. contg. a further hetero atom or carrying a fused benzene ring; R = H and R = lower alkyl; or R +R = H; halo;etc.; and C atom gamma has the S configuration when R is other than H.

公开(公告)号：PL307711A1

公开(公告)日：1995-09-18

申请号：PL30771195

申请日：1995-03-15

Applicant: HOFFMANN LA ROCHE

Inventor： GODEL THIERRY ,  HUNKELER WALTER ,  STADLER HEINZ ,  WIDMER ULRICH

IPC: A61K20060101 ,  A61K31/41 ,  A61K31/55 ,  C07D20060101 ,  C07D487/04 ,  C07D487/12 ,  C07D491/12 ,  C07D495/12 ,  C07D495/14

公开(公告)号：CA2143246A1

公开(公告)日：1995-09-17

申请号：CA2143246

申请日：1995-02-23

Applicant: HOFFMANN LA ROCHE

Inventor： GODEL THIERRY ,  HUNKELER WALTER ,  STADLER HEINZ ,  WIDMER ULRICH

IPC: A61K31/41 ,  A61K31/55 ,  A61K31/5517 ,  A61P21/02 ,  A61P25/08 ,  A61P25/20 ,  A61P43/00 ,  C07D487/02 ,  C07D487/04 ,  C07D495/12 ,  C07D495/14 ,  C07D498/14 ,  C07D487/14 ,  C07D495/22

Abstract: Aminomethyl-substd. oxadiazolyl-imidazodiazepines of formula (I) and their addn salts are new: A and C atoms alpha and beta form a gp of formula e.g. (A ):Q = a gp. of formula e.g. (Q ):R , R = H; lower alkyl,etc.;or NR R = 5-8 membered heterocycle opt. contg. a further hetero atom or carrying a fused benzene ring; R = H and R = lower alkyl; or R +R = H; halo;etc.; and C atom gamma has the S configuration when R is other than H.