公开(公告)号：JP2008169206A

公开(公告)日：2008-07-24

申请号：JP2007325072

申请日：2007-12-17

Applicant: F Hoffmann La Roche Ag ,  エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft

Inventor： MUTEL VINCENT ,  PETERS JENS-UWE ,  WICHMANN JUERGEN

IPC: C07D209/14 ,  C07D233/64 ,  A61K31/4045 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/4164 ,  A61K31/4174 ,  A61K31/4178 ,  A61K31/4245 ,  A61K31/437 ,  A61K31/4985 ,  A61K31/5383 ,  A61K31/542 ,  A61P1/08 ,  A61P9/02 ,  A61P9/10 ,  A61P13/02 ,  A61P19/08 ,  A61P21/02 ,  A61P21/04 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/34 ,  A61P25/36 ,  A61P27/02 ,  A61P31/18 ,  A61P43/00 ,  C07D209/16 ,  C07D231/12 ,  C07D233/54 ,  C07D233/58 ,  C07D233/68 ,  C07D233/90 ,  C07D233/92 ,  C07D233/94 ,  C07D403/06 ,  C07D403/10 ,  C07D413/04 ,  C07D491/147 ,  C07D495/14 ,  C07D498/04 ,  C07D513/14

CPC classification number: C07D233/56 ,  A61K31/4164 ,  C07D209/14 ,  C07D233/64 ,  C07D233/90 ,  C07D233/92 ,  C07D233/94 ,  C07D403/06 ,  C07D413/04 ,  C07D513/14

Abstract: PROBLEM TO BE SOLVED: To provide a novel glutamate receptor antagonist. SOLUTION: The present invention retates to the use of a compound represented by formula (I) [wherein R 1 , R 2 , R 3 , R 4 and R 5 each independently represent hydrogen, a lower alkyl, a -(CH 2 ) n -halogen, a lower alkoxy, a -(CH 2 ) n -NRR', a -(CH 2 ) n -N(R)-C(O)-lower alkyl, an aryl or a heteroaryl which is not substituted or substituted with one or more lower alkyl residues, and A represents -CH=CH- or -C≡C-] or a pharmaceutically acceptable salt thereof for producing a pharmaceutical agent for treatment or prevention of mGluR5 receptor mediated disorders. COPYRIGHT: (C)2008,JPO&INPIT

Abstract translation: 待解决的问题：提供新的谷氨酸受体拮抗剂。 解决方案：本发明重述由式（I）表示的化合物[其中R 1，R 2，R 3，R 3， SP>，R 4 和R 5 各自独立地表示氢，低级烷基， - （CH 2 ）< SB>卤素，低级烷氧基， - （CH 2 ） -NRR'，a - （CH 2 N（R）-C（O） - 低级烷基，未被一个或多个低级烷基残基取代或取代的芳基或杂芳基，A表示-CH = CH-或-C≡ C-]或其药学上可接受的盐，用于制备用于治疗或预防mGluR5受体介导的病症的药剂。 版权所有（C）2008，JPO＆INPIT

公开(公告)号：JPH1171380A

公开(公告)日：1999-03-16

申请号：JP19936398

申请日：1998-07-15

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  KOLCZEWSKI SABINE ,  MUTEL VINCENT ,  WICHMANN JUERGEN ,  WOLTERING THOMAS JOHANNES

IPC: C07D239/22 ,  A61K31/00 ,  A61K31/505 ,  A61K31/519 ,  A61P1/08 ,  A61P9/00 ,  A61P13/02 ,  A61P15/00 ,  A61P25/00 ,  A61P25/04 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  A61P25/30 ,  A61P27/02 ,  A61P43/00 ,  C07D239/00 ,  C07D239/40 ,  C07D277/00 ,  C07D513/04

Abstract: PROBLEM TO BE SOLVED: To obtain the subject novel compound that is useful as a therapeutic and preventive agent for cerebral function restriction caused by transplantation, head injury, cardiac arrest, acute and/or chronic neurological disorders as an antagonist of metabotropic glutamate receptor and/or as an agonist. SOLUTION: This compound is represented by formula I (R is H, a lower alkoxy or the like; R is a lower alkyl, a lower alkoxy or the like; R -R are each H, a halogen or the like) or its salt, typically (RS)-2-(2,6- dichlorophenyl)-5-(2-methoxyphenyl)-7-methyl-5H-thiazolo [3,2- a]pyrimidine-6-carboxylic 2-dimethylaminoethyl ester. This compound is prepared by reaction of a compound of formula II with α-bromo-acetaldehyde, when necessary, in addition, converting the compound of formula I to its salt. The intermediate compound of formula II is novel and is prepared, for example, by reaction of 4-metoxybenzaldehyde with acetylacetone and thiourea.

公开(公告)号：JP2000086597A

公开(公告)日：2000-03-28

申请号：JP24416799

申请日：1999-08-31

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  HUGUENIN-VIRCHAUX PHILIPPE N ,  MUTEL VINCENT ,  STADLER HEINZ ,  WOLTERING THOMAS JOHANNES

IPC: A61K31/00 ,  A61K31/196 ,  A61P25/00 ,  A61P25/18 ,  C07C227/16 ,  C07C227/32 ,  C07C229/50 ,  C07C247/14

Abstract: PROBLEM TO BE SOLVED: To readily obtain the subject compound useful as a ligand for a metabotropic glutamate receptor of group II in high yield in a diastereomeric and enantiomeric purity by using a specific intermediate. SOLUTION: The carbonyl group of a compound of formula I (R" and R"' are each benzyl or a lower alkyl) is reduced to a hydroxyl group to give a compound or formula II or III. If desired, the compound of formula II is alkylated, alkenylated or benzylated, the azido group is reduced to an amino group and the ester group is hydrolysed. The double bond of the obtained compound is hydrogenated using, if desired, a tritium gas to give a compound of formula IV (R1 is hydroxyl, a lower alkoxy, a lower alkenyloxy, benzyloxy, H or the like; R11 is H, a deuterium atom, a tritium atom or the like; R2 is H or the like). As a result, a compound useful for suppression of a neurological symptom and a psychiatric disease is provided.

公开(公告)号：JP2001089472A

公开(公告)日：2001-04-03

申请号：JP2000236848

申请日：2000-08-04

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  BINGGELI ALFRED ,  MAERKI HANS-PETER ,  MUTEL VINCENT ,  WILHELM MAURICE ,  WOSTL WOLFGANG

IPC: C07D223/16 ,  A61K31/55 ,  A61P1/08 ,  A61P3/08 ,  A61P9/04 ,  A61P9/10 ,  A61P13/10 ,  A61P21/02 ,  A61P25/06 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P25/34 ,  A61P27/02 ,  A61P43/00 ,  C07D223/04 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D471/04 ,  C07D487/04 ,  C07D521/00 ,  C07F7/18

Abstract: PROBLEM TO BE SOLVED: To provide an antagonist of metabotropic glutamate receptor. SOLUTION: The compound of the formula I, and a salt thereof pharmaceutically acceptable as a pharmaceutically active material are provided. A method for preparing them, a medicine based on the compound, a method for preparing the medicine, the use of the compound in the suppression or prevention of a disease, and the use in the preparation of the medicine corresponding thereto are also provided. The preferable compound in the compounds of the formula I is the one of the formula I wherein R1 is =O and R2 is CN, e.g. 3-ethyl-2- methyl-5-nitro-6-(1,2,4,5-tetrahydro-benz[d]azepin-3-yl)-3H-pyrimidin- 4-one and 2-amino-6-oxo-4-(1,2,4,5-tetrahydro-benz[d]azepin-3-yl)-1,6-dihydro-py rimidine-5- carbonitrile.

公开(公告)号：WO0129011A3

公开(公告)日：2001-11-08

申请号：PCT/EP0009553

申请日：2000-09-29

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  ALANINE ALEXANDER ,  GOETSCHI ERWIN ,  MUTEL VINCENT ,  WOLTERING THOMAS JOHANNES

IPC: A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61P1/08 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P13/00 ,  A61P21/02 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/34 ,  A61P25/36 ,  A61P27/02 ,  A61P43/00 ,  C07D243/12 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14 ,  C07D403/10 ,  C07D403/14 ,  C07D405/04 ,  C07D405/06 ,  C07D409/04 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D417/04 ,  C07D417/10 ,  C07D417/14 ,  C07D491/056 ,  C07D491/113 ,  C07F7/10

CPC classification number: C07D243/12

Abstract: The present invention relates to compounds of general formula (I) wherein X is a single bond or an ethynediyl group, wherein, in case X is a single bond, R is halogen or phenyl which is optionally substituted with halogen, lower alkyl, halo-lower alkyl, lower alkoxy, halo-lower alkoxy, or cyano; In case X is an ethynediyl group, R is phenyl, optionally substituted with halogen, lower alkyl, halo-lower alkyl, lower cycloalkyl, lower alkoxy or halo-lower alkoxy; R is a 5 or 6 membered aryl or heteroaryl which are optionally substituted. The compounds according to the present invention can be used for treating or preventing acute and/or chronic neurological disorders such as psychosis, schizophrenia, Alzheimer's disease, cognitive disorders and memory deficits.

Abstract translation: 本发明涉及通式（I）的化合物，其中X为单键或亚乙二基，其中，在X为单键的情况下，R 1为卤素或任选被卤素取代的苯基，低级烷基 ，卤代低级烷基，低级烷氧基，卤代低级烷氧基或氰基; 在X为乙炔二基的情况下，R 1为苯基，任选被卤素，低级烷基，卤代低级烷基，低级环烷基，低级烷氧基或卤代低级烷氧基取代; R 3是任选被取代的5或6元芳基或杂芳基。 根据本发明的化合物可用于治疗或预防急性和/或慢性神经障碍，例如精神病，精神分裂症，阿尔茨海默病，认知障碍和记忆缺陷。

公开(公告)号：WO0129012A3

公开(公告)日：2001-11-08

申请号：PCT/EP0009554

申请日：2000-09-29

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  ALANINE ALEXANDER ,  GOETSCHI ERWIN ,  MUTEL VINCENT ,  WOLTERING THOMAS JOHANNES

IPC: A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61P1/08 ,  A61P3/08 ,  A61P9/08 ,  A61P13/02 ,  A61P21/02 ,  A61P21/04 ,  A61P25/00 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/34 ,  A61P25/36 ,  A61P27/02 ,  A61P29/02 ,  A61P43/00 ,  C07D243/12 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14 ,  C07D403/10 ,  C07D405/04 ,  C07D405/06 ,  C07D409/04 ,  C07D409/08 ,  C07D409/14 ,  C07D413/10 ,  C07D417/02 ,  C07D417/04 ,  C07D417/06 ,  C07D417/10 ,  C07D417/14 ,  C07F7/10

CPC classification number: C07D401/04 ,  C07D243/12 ,  C07D403/10 ,  C07D405/06 ,  C07D413/10 ,  C07D417/06 ,  C07D417/10

Abstract: The present invention relates to compounds of general formula (I) wherein R is phenyl; pyridine; thiophenyl or thiazolyl, which are optionally substituted. The compounds according to the present invention can be used for treating or preventing acute and/or chronic neurological disorders such as psychosis, schizophrenia, Alzheimer's disease, cognitive disorders and memory deficits.

Abstract translation: 本发明涉及通式（I）的化合物，其中R 3是苯基; 吡啶; 噻吩基或噻唑基，其任选被取代。 根据本发明的化合物可用于治疗或预防急性和/或慢性神经障碍，例如精神病，精神分裂症，阿尔茨海默病，认知障碍和记忆缺陷。

公开(公告)号：CA2430696C

公开(公告)日：2009-01-27

申请号：CA2430696

申请日：2001-11-26

Applicant: HOFFMANN LA ROCHE

Inventor： WICHMANN JUERGEN ,  PETERS JENS-UWE ,  MUTEL VINCENT

IPC: C07D233/64 ,  C07D233/90 ,  A61K31/404 ,  A61K31/4045 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4174 ,  A61K31/4178 ,  A61K31/4245 ,  A61K31/437 ,  A61K31/4985 ,  A61K31/5383 ,  A61K31/542 ,  A61P1/08 ,  A61P9/02 ,  A61P9/10 ,  A61P13/00 ,  A61P13/02 ,  A61P21/02 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/34 ,  A61P25/36 ,  A61P31/18 ,  A61P43/00 ,  C07D209/14 ,  C07D209/16 ,  C07D231/12 ,  C07D233/54 ,  C07D233/56 ,  C07D233/58 ,  C07D233/68 ,  C07D233/92 ,  C07D233/94 ,  C07D403/06 ,  C07D403/10 ,  C07D413/04 ,  C07D491/147 ,  C07D495/14 ,  C07D498/04 ,  C07D513/14

Abstract: This invention relates to the use of compounds of formula (I) wherein R1, R2 , R3, R4 and R5 are as defined in the description, A signifies -CH=CH- or -C=C -; and B signifies (B1); (B2); (B3); (B4); (B5) or (B6); wherein R6 to R26, X a nd Y have the significances given in the description, as well as pharmaceutical ly acceptable salts thereof, for the manufacture of medicaments for the treatme nt or prevention of mGluR5 receptor mediated disorders.

公开(公告)号：NO324326B1

公开(公告)日：2007-09-24

申请号：NO20032503

申请日：2003-06-03

Applicant: HOFFMANN LA ROCHE

Inventor： WICHMANN JUERGEN ,  MUTEL VINCENT ,  PETERS JENS-UWE

IPC: C07D233/64 ,  C07D233/90 ,  A61K31/4045 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4174 ,  A61K31/4178 ,  A61K31/4245 ,  A61K31/437 ,  A61K31/4985 ,  A61P1/08 ,  A61P9/02 ,  A61P9/10 ,  A61P13/02 ,  A61P21/02 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/34 ,  A61P25/36 ,  A61P31/18 ,  A61P43/00 ,  C07D209/14 ,  C07D209/16 ,  C07D231/12 ,  C07D233/54 ,  C07D233/58 ,  C07D233/68 ,  C07D233/92 ,  C07D233/94 ,  C07D403/06 ,  C07D403/10 ,  C07D413/04 ,  C07D491/147 ,  C07D495/14 ,  C07D498/04 ,  C07D513/14

Abstract: This invention relates to a compound and the use of the compound of the formula wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the description, A signifies -CH-CH- or -C≡C-; and B signifies wherein R 6 to R 26 , X and Y are as defined in the specification or a pharmaceutically acceptable salt thereof, for use in pharmaceutical compositions for the treatment or prevention of mGluR5 receptor mediated disorders.

公开(公告)号：NO324218B1

公开(公告)日：2007-09-10

申请号：NO20026263

申请日：2002-12-27

Applicant: HOFFMANN LA ROCHE

Inventor： WICHMANN JUERGEN ,  MUTEL VINCENT

IPC: C07D401/12 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/41 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/4245 ,  A61K31/4439 ,  A61K31/506 ,  A61P1/08 ,  A61P3/08 ,  A61P9/00 ,  A61P9/02 ,  A61P13/02 ,  A61P19/00 ,  A61P21/00 ,  A61P21/02 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/34 ,  A61P25/36 ,  A61P27/02 ,  A61P31/12 ,  A61P39/00 ,  A61P41/00 ,  A61P43/00 ,  C07D207/48 ,  C07D403/04 ,  C07D403/06 ,  C07D413/04 ,  C07D413/06 ,  C07D521/00

Abstract: The present invention is a series of compounds that are derivatives of 1-sulfonyl-pyrrolidine and that demonstrate affinity towards metabotropic glutamate receptors. The invention further relates to medicaments containing these compounds and to a process for their preparation. The compounds possess affinity towards metabotropic glutamate receptors and are therefore useful in the treatment or prevention of acute and/or chronic neurological disorders.

公开(公告)号：ES2274038T3

公开(公告)日：2007-05-16

申请号：ES02738077

申请日：2002-05-16

Applicant: HOFFMANN LA ROCHE

Inventor： MUTEL VINCENT ,  PETERS JENS-UWE ,  WICHMANN JUERGEN

IPC: C07D239/46 ,  C07D239/47 ,  A61K31/505 ,  A61K31/506 ,  A61P1/00 ,  A61P1/16 ,  A61P3/10 ,  A61P9/10 ,  A61P13/02 ,  A61P13/12 ,  A61P19/02 ,  A61P19/06 ,  A61P21/00 ,  A61P21/02 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/34 ,  A61P25/36 ,  A61P27/02 ,  A61P29/00 ,  A61P29/02 ,  A61P31/18 ,  A61P35/00 ,  A61P43/00 ,  C07D403/06 ,  C07D405/06 ,  C07D409/06 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14

Abstract: El uso de un compuesto de fórmula general en donde R1 significa C2-C6-alquenilo, C2-C6-alquinilo, C3-C6-cicloalquilo, -C(O)O-(C1-C6)-alquilo, -C(O)O-(C2-C6)-alquenilo, -C(O)O-(C2-C6)-alquinilo, -C(O)O-(C3-C6)-cicloalquilo o -C(O)O-CH2-(C3-C6)-cicloalquilo, en donde el anillo cicloalquilo puede estar sustituido por uno o más C1-C6-alquilo, -C(O)O-CH2-heteroarilo, en donde el anillo heteroarilo puede estar sustituido por uno o más C1-C6-alquilo, o heteroarilo sin sustituir o heteroarilo sustituido por uno o más C1-C6-alquilo, C2-C6-alquenilo, C2-C6-alquinilo, C3-C6-cicloalquilo o halógeno; R2 significa hidrógeno o C1-C6-alquilo; R3 significa arilo sin sustituir o arilo sustituido por uno o más C1-C6-alquilo, C2-C6-alquenilo, C2-C6-alquinilo, C3-C6-cicloalquilo, halógeno o ciano, o heteroarilo sin sustituir o heteroarilo sustituido por uno o más C1-C6-alquilo, C2-C6-alquenilo, C2-C6-alquinilo, C3-C6-cicloalquilo, halógeno o ciano, o -C(O)O-(C1-C6)-alquilo; R4 significa hidrógeno o C1-C6-alquilo; y m es 0, 1 ó 2; así como las sales farmacéuticamente aceptables de los mismos para la fabricación de medicamentos para el tratamiento y prevención de trastornos cognitivos; deficits de memoria; dolor agudo y crónico; pérdida de la función cerebral causada por operaciones de by-pass o trasplantes, bajo riego sanguíneo al cerebro, lesiones en la médula espinal, lesiones cerebrales, hipoxia causada por embarazo, paro cardíaco e hipoglicemia; trastornos neurológicos agudos y crónicos comprendiendo epilepsia, esquizofrenia, ansiedad, procesos degenerativos agudos, traumáticos o crónicos del sistema nervioso que comprenden enfermedad de Alzheimer, demencia senil, corea de Huntington, (ELA), esclerosis múltiple, demencia causada por SIDA, daños oculares, retinopatía, parkinsonismo idiopático o parkinsonismo causado por medicamentos así como enfermedades que conducen a funciones de deficiencia de glutamato, tales como por ejemplo espasmos musculares, convulsiones, migraña, incontinencia urinaria, adicción a la nicotina, adicción a opiácios, ansiedad, vómitos, disquinesia y depresiones.