公开(公告)号：WO02066449A2

公开(公告)日：2002-08-29

申请号：PCT/EP0201666

申请日：2002-02-14

Applicant: SOLVAY PHARM BV ,  AAR MARCEL P M VAN ,  SCHOUTEN STEFANUS J ,  ZORGDRAGER JAN ,  HESLINGA MICHIEL C

Inventor： AAR MARCEL P M VAN ,  SCHOUTEN STEFANUS J ,  ZORGDRAGER JAN ,  HESLINGA MICHIEL C

IPC: C07D263/58

CPC classification number: C07D263/58

Abstract: The invention relates to the mesylates of a group of piperazine derivatives and to a process for the preparation of these mesylates in an economic way in the high yield and of high purity. According to the process of the invention the synthesis of the piperazine ring and the mesylate formation are combined in a single reaction step. The invention relates to the mesylate of compounds of the formula (I) wherein X is a bicyclic heterocyclic phenyl group and Y is methyl, ethyl (optionally substituted with fluorine), cycloalkyl (3-7C) methyl, benzyl or m-phenyl benzyl.

Abstract translation: 本发明涉及一组哌嗪衍生物的甲磺酸酯以及以高产率和高纯度以经济方式制备这些甲磺酸酯的方法。 根据本发明的方法，哌嗪环和甲磺酸酯形成物的合成在单个反应步骤中组合。 本发明涉及式（I）化合物的甲磺酸酯，其中X是双环杂环苯基，Y是甲基，乙基（任选被氟取代），环烷基（3-7C）甲基，苄基或间苯基苄基。

公开(公告)号：WO2008034863A3

公开(公告)日：2008-05-08

申请号：PCT/EP2007059944

申请日：2007-09-20

Applicant: SOLVAY PHARM BV ,  IWEMA BAKKER WOUTER I ,  KEIZER HISKIAS G ,  NEUT VAN DER MARTINA A W ,  KRUSE CORNELIS G ,  LOEVEZIJN VAN ARNOLD ,  ZORGDRAGER JAN

Inventor： IWEMA BAKKER WOUTER I ,  KEIZER HISKIAS G ,  NEUT VAN DER MARTINA A W ,  KRUSE CORNELIS G ,  LOEVEZIJN VAN ARNOLD ,  ZORGDRAGER JAN

IPC: C07D231/06 ,  A61K31/415 ,  A61K31/4155 ,  A61P25/00 ,  C07D231/12 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D407/04 ,  C07D407/12 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12 ,  C07D513/04

CPC classification number: C07D513/04 ,  A61K9/0019 ,  A61K9/0031 ,  A61K9/1652 ,  A61K9/2054 ,  C07D231/06 ,  C07D231/12 ,  C07D231/54 ,  C07D231/56 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/04 ,  C07D405/10 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04 ,  C07D471/10 ,  C07D491/10 ,  C07D491/107 ,  C07D519/00

Abstract: This invention concerns sulfonylpyrazoline carboxamidine derivatives as antagonists of 5-HT 6 receptors, to methods for the preparation of these compounds and to novel intermediates useful for their synthesis. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes. The compounds have the general formula (1), wherein the symbols have the meanings given in the description.

Abstract translation: 本发明涉及作为5-HT 6受体拮抗剂的磺酰吡唑啉甲脒衍生物，涉及制备这些化合物的方法和用于它们合成的新型中间体。 本发明还涉及这些化合物和组合物的用途，特别是它们在给予患者以在帕金森病，亨廷顿氏舞蹈症，精神分裂症，焦虑症，抑郁症，躁狂抑郁症，精神病，癫痫，强迫症中的治疗效果方面的用途， 情绪障碍，偏头痛，阿尔茨海默病，年龄相关认知衰退，轻度认知障碍，睡眠障碍，进食障碍，厌食症，贪食症，暴饮暴食症，惊恐发作，静坐不动，注意力缺陷多动障碍，注意力缺陷障碍，可卡因滥用 ，乙醇，尼古丁或苯并二氮杂，疼痛，与脊髓损伤或头部损伤相关的疾病，脑积水，功能性肠病，肠易激综合征，肥胖症和2型糖尿病。 化合物具有通式（1），其中符号具有说明书中给出的含义。

公开(公告)号：BRPI0716860A2

公开(公告)日：2013-10-15

申请号：BRPI0716860

申请日：2007-09-20

Applicant: SOLVAY PHARM BV

Inventor： BAKKER WOUNTER I IWEMA ,  KAIZER HISKIAS G ,  VAN DER NEUT MARTINA A W ,  KRUSE CORNELIS G ,  VAN LOEVEZIJIN ARNOLD ,  ZORGDRAGER JAN

IPC: C07D231/06 ,  A61K31/415 ,  A61K31/4155 ,  A61P25/00 ,  C07D231/12 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D407/04 ,  C07D407/12 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12 ,  C07D513/04

Abstract: This invention concerns compounds of the general formula (1): and derivatives thereof, which are antagonists of 5-HT6 receptors, wherein the symbols have the meanings given in the description. The invention also concerns methods for the preparation of these compounds, to novel intermediates useful for their synthesis, and to uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in treating at least on disease or condition chosen from Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes.

公开(公告)号：AU2007298987B2

公开(公告)日：2012-10-04

申请号：AU2007298987

申请日：2007-09-20

Applicant: SOLVAY PHARM BV

Inventor： KRUSE CORNELIS G ,  KEIZER HISKIAS G ,  ZORGDRAGER JAN ,  LOEVEZIJN VAN ARNOLD ,  NEUT VAN DER ,  IWEMA BAKKER WOUTER I

IPC: C07D231/06 ,  A61K31/415 ,  A61K31/4155 ,  A61P25/00 ,  C07D231/12 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D407/04 ,  C07D407/12 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12 ,  C07D513/04

Abstract: This invention concerns sulfonylpyrazoline carboxamidine derivatives as antagonists of 5-HT receptors, to methods for the preparation of these compounds and to novel intermediates useful for their synthesis. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes. The compounds have the general formula (1), wherein the symbols have the meanings given in the description.

公开(公告)号：CZ301780B6

公开(公告)日：2010-06-23

申请号：CZ2003697

申请日：2002-02-14

Applicant: SOLVAY PHARM BV

Inventor： VAN AAR MARCEL P M ,  SCHOUTEN STEFANUS J ,  ZORGDRAGER JAN ,  HESLINGA MICHIEL C

IPC: C07D403/04 ,  C07D263/58 ,  C07D407/04 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D419/04

Abstract: Jednostupnová reakce prípravy mesylátových piperazinových derivátu obecného vzorce 1, kde X je bicyklický zbytek vzorce 4, v nemž R.sub.1.n. je vodík nebo fluor, R.sub.2.n. je vodík, C1-C4 alkyl, C1-C4 alkoxyl nebo oxoskupina a A je 5 až 7clenný heterocyklus s 1 až 3 heteroatomy vybranými z kyslíku, dusíku a síry, a Y je methyl, poprípade fluorsubstituovaný ethyl nebo (C3-C7) cykloalkylmethyl, nebo poprípade substituovaný benzyl, reakcí aminu X-NH.sub.2.n. se slouceninou vzorce 3 a anhydridem methansulfonové kyseliny. Mesylátové slouceniny vzorce 1 tímto zpusobem pripravené.

公开(公告)号：AR062907A1

公开(公告)日：2008-12-17

申请号：ARP070104142

申请日：2007-09-19

Applicant: SOLVAY PHARM BV

Inventor： VAN DER NEUT MARTINA A W ,  VAN LOEVEZIJN ARNOLD ,  ZORGDRAGER JAN ,  IWENA BAKKER WOUTER I ,  KRUSE CORNELIS G ,  KEIZER HISKIAS G

IPC: C07D231/06 ,  C07D401/12 ,  C07D231/54 ,  C07D409/12 ,  C07D401/04 ,  C07D409/04 ,  C07D405/04 ,  C07D471/04 ,  C07D491/107 ,  C07D417/12 ,  C07D413/14 ,  A61K31/415 ,  A61K31/416 ,  A61K31/4162 ,  A61P25/00

Abstract: La presente se refiere a métodos para la preparacion de estos compuestos y a nuevos compuestos intermedios utiles para su síntesis. También se refiere a los usos de tales compuestos y composiciones, particularmente su uso en la administracion de los mismos a pacientes para lograr un efecto terapéutico en la enfermedad de Parkinson, corea de Huntington, esquizofrenia, ansiedad, depresion, depresion maníaca, psicosis, epilepsia, trastornos compulsivos obsesivos, trastornos emocionales, migrana, enfermedad de Alzheimer, declinacion cognitiva relacionada con la edad, dano cognitivo suave, trastornos del sueno, trastornos alimenticios, anorexia, bulimia, trastornos de comer en exceso, ataques de pánico, acatisia, trastorno de déficit de atencion por hiperactividad, trastorno de déficit de atencion, supresion del abuso de cocaína, etanol, nicotina o benzodiazepinas, dolor, trastornos asociados con trauma espinal o lesion de la cabeza, .hidrocefálea, trastorno funcional del intestino, síndrome de intestino irritable, obesidad y diabetes tipo 2. Reivindicacion 1: Un compuesto derivado de sulfonilpirazolincarboxamidina, caracterizado por la formula (1): o un tautomero, estereoisomero, N-oxido, análogo marcado isotopicamente o una sal, hidrato o solvato farmacologicamente aceptable de cualquiera de los precedentes, donde: R1 representa hidrogeno, un grupo alquilo C1-4 insustituido, un grupo alquilo C1-4 sustituido con uno o más átomos de halogeno, o un grupo fenilo opcionalmente sustituido con uno o más átomos de halogeno, R2 y R3 representan independientemente hidrogeno, un grupo alquilo C1-4 insustituido, un grupo alquilo C1-4 sustituido con uno o más átomos de halogeno, un grupo alquil C1-4-O- alquil-C1-4-fenilo, opcionalmente sustituido con uno o más átomos de halogeno, o un grupo fenilo, opcionalmente sustituido con uno o más átomos de halogeno, o R1 y R2, conjuntamente con los átomos de carbono marcados 'a' y 'b' forman un anillo cicloalquilo C5-8, o R2 y R3, conjuntamente con el átomo de carbono marcado 'b' forman un anillo cicloalquilo C3-8, o R2 y R3, conjuntamente con el átomo de carbono marcado 'b' forman un anillo heterocicloalquilo C5-8 opcionalmente sustituido, o R4 y R5 representan independientemente hidrogeno, un grupo alquilo C1-4 insustituido, un grupo alquilo C1-4 sustituido con uno o más átomos de halogeno, un grupo aromático monociclico opcionalmente sustituido, un grupo aromático bicíclico fusionado opcionalmente sustituido, un grupo heteroaromático monocíclico opcionalmente sustituido, un grupo heteroaromático bicíclico fusionado opcionalmente sustituido, o R3 y R4, conjuntamente con los átomos de carbono marcados 'b' y 'c' forman un anillo cicloalquilo C3-8, o R3 y R4, conjuntamente con los átomos de C marcados 'b' y 'c' forman un anillo heterocicloalquilo C5-8 opcionalmente sustituido, o R6 y R7 representan independientemente un átomo de hidrogeno, o un grupo alquilo C1-4, o un grupo alquilo C1-4 sustituido con uno o más átomos de halogeno; o un grupo alcoxi C1-3, o un grupo dialquil C1-3-amino-alquilo C1-3, o un grupo aromático o heteroaromático monocíclico o bicíclico fusionado opcionalmente sustituido, o un grupo cicloalquilo C5-8 opcionalmente sustituido o un grupo heterocicloalquilo C5-8 o opcionalmente sustituido, o R6 y R7, conjuntamente con el átomo de nitrogeno al cual están unidos, forman un grupo heterocicloalquilo C5-8 opcionalmente sustituido, R8 representa un grupo aromático monocíclico opcionalmente sustituido, un grupo aromático bicíclico fusionado opcionalmente sustituido, un grupo heteroaromático monocíclico opcionalmente sustituido, un grupo heteroaromático bicíclico fusionado opcionalmente sustituido, un grupo -CR9=CR10-arilo donde R9 y R10 representan independientemente hidrogeno o un grupo alquilo C1-3, un grupo -C:::C-arilo, un grupo piperidinilo opcionalmente sustituido, o un grupo -NR11R12, donde R11 y R12 representan independientemente hidrogeno, un grupo alquilo C1-3 o un grupo fenilo o bencilo opcionalmente sustituido.

公开(公告)号：CA2662484A1

公开(公告)日：2008-03-27

申请号：CA2662484

申请日：2007-09-20

Applicant: SOLVAY PHARM BV

Inventor： ZORGDRAGER JAN ,  VAN LOEVEZIJN ARNOLD ,  KRUSE CORNELIS G ,  VAN DER NEUT MARTINA A W ,  KEIZER HISKIAS G ,  IWEMA BAKKER WOUTER I

IPC: C07D231/06 ,  A61K31/415 ,  A61K31/4155 ,  A61P25/00 ,  C07D231/12 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D407/04 ,  C07D407/12 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12 ,  C07D513/04

Abstract: This invention concerns sulfonylpyrazoline carboxamidine derivatives as a ntagonists of 5-HT6 receptors, to methods for the preparation of these compo unds and to novel intermediates useful for their synthesis. The invention al so relates to the uses of such compounds and compositions, particularly thei r use in administering them to patients to achieve a therapeutic effect in P arkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mi ld cognitive impairment, sleep disorders, eating disorders, anorexia, bulimi a, binge eating disorders, panic attacks, akathisia, attention deficit hyper activity disorder, attention deficit disorder, withdrawal from abuse of coca ine, ethanol, nicotine or benzodiazepines, pain, disorders associated with s pinal trauma or head injury, hydrocephalus, functional bowel disorder, Irrit able Bowel Syndrome, obesity and type-2 diabetes. The compounds have the gen eral formula (1), wherein the symbols have the meanings given in the descrip tion.

公开(公告)号：HU0400772A2

公开(公告)日：2004-08-30

申请号：HU0400772

申请日：2002-02-14

Applicant: SOLVAY PHARM BV

Inventor： VAN AAR MARCEL P M ,  HESLINGA MICHIEL C ,  SCHOUTEN STEFANUS J ,  ZORGDRAGER JAN

IPC: C07D263/58

Abstract: The invention relates to the mesylates of a group of piperazine derivatives and to a process for the preparation of these mesylates in an economic way in the high yield and of high purity. According to the process of the invention the synthesis of the piperazine ring and the mesylate formation are combined in a single reaction step. The invention relates to the mesylate of compounds of the formula (I) wherein X is a bicyclic heterocyclic phenyl group and Y is methyl, ethyl (optionally substituted with fluorine), cycloalkyl (3-7C) methyl, benzyl or m-phenyl benzyl

公开(公告)号：HK1059934A1

公开(公告)日：2004-07-23

申请号：HK04102835

申请日：2004-04-22

Applicant: SOLVAY PHARM BV

Inventor： AAR VAN MARCEL P M ,  SCHOUTEN STEFANUS J ,  ZORGDRAGER JAN ,  HESLINGA MICHIEL C

IPC: C07D263/58 ,  C07D

Abstract: The invention relates to the mesylates of a group of piperazine derivatives and to a process for the preparation of these mesylates in an economic way in the high yield and of high purity. According to the process of the invention the synthesis of the piperazine ring and the mesylate formation are combined in a single reaction step. The invention relates to the mesylate of compounds of the formula (I) wherein X is a bicyclic heterocyclic phenyl group and Y is methyl, ethyl (optionally substituted with fluorine), cycloalkyl (3-7C) methyl, benzyl or m-phenyl benzyl

公开(公告)号：ZA200301590B

公开(公告)日：2004-02-05

申请号：ZA200301590

申请日：2003-02-26

Applicant: SOLVAY PHARM BV

Inventor： AAR MARCEL P M VAN ,  ZORGDRAGER JAN ,  SCHOUTEN STEFANUS J ,  HESLINGA MICHIEL C

IPC: C07D263/58 ,  C07D

Abstract: The invention relates to the mesylates of a group of piperazine derivatives and to a process for the preparation of these mesylates in an economic way in the high yield and of high purity. According to the process of the invention the synthesis of the piperazine ring and the mesylate formation are combined in a single reaction step. The invention relates to the mesylate of compounds of the formula (I) wherein X is a bicyclic heterocyclic phenyl group and Y is methyl, ethyl (optionally substituted with fluorine), cycloalkyl (3-7C) methyl, benzyl or m-phenyl benzyl