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：WO2006089861A3

公开(公告)日：2006-10-26

申请号：PCT/EP2006060060

申请日：2006-02-17

Applicant: SOLVAY PHARM BV ,  DRUKARCH BENJAMIN ,  SCHOFFELMEER ANTON N M ,  FEENSTRA ROELOF W ,  CHRISTEN MARIE-ODILE ,  BURGOT JEAN-LOUISE ,  CHOLLET MARYLENE ,  IWEMA BAKKER WOUTER I ,  VAN VLIET BERNARD J ,  TULP MARTINUS TH M

Inventor： DRUKARCH BENJAMIN ,  SCHOFFELMEER ANTON N M ,  FEENSTRA ROELOF W ,  CHRISTEN MARIE-ODILE ,  BURGOT JEAN-LOUISE ,  CHOLLET MARYLENE ,  IWEMA BAKKER WOUTER I ,  VAN VLIET BERNARD J ,  TULP MARTINUS TH M

IPC: C07D339/04 ,  A61K31/385

CPC classification number: C07D409/12 ,  A61K31/385 ,  C07D339/04

Abstract: The invention relates to dithiolethiones derivatives as monoamino oxidase inhibitors, in particular MAO-B inhibitors, to methods for the preparation of these compounds and to novel intermediates useful for the synthesis of said dithiolethiones derivatives. The invention also relates to the use of a compound disclosed herein for the manufacture of a medicament giving a beneficial effect. In embodiments of the invention specific compounds disclosed herein are used for the manufacture of a medicament useful in the treatment, amelioration or prevention of conditions associated with dysfunction of monoamine neurotransmission. The compounds have the general formula (1) wherein the symbols have the meanings given in the specification.

Abstract translation: 本发明涉及二硫代硫代乙烯衍生物作为单氨基氧化酶抑制剂，特别是MAO-B抑制剂，涉及制备这些化合物的方法和用于合成所述二硫代硫代衍生物的新型中间体。 本发明还涉及本文公开的化合物在制备产生有益效果的药物中的用途。 在本发明的实施方案中，本文公开的具体化合物用于制备可用于治疗，改善或预防与单胺神经传递功能障碍相关的病症的药物。 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：UA98122C2

公开(公告)日：2012-04-25

申请号：UAA200903909

申请日：2007-09-20

Applicant: SOLVAY PHARM BV

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

公开(公告)号：ZA200706258B

公开(公告)日：2009-08-26

申请号：ZA200706258

申请日：2007-07-27

Applicant: SOLVAY PHARM BV

Inventor： BENJAMIN DRUKARCH ,  FEENSTRA ROELOF W ,  JEAN-LOUISE BURGOT ,  IWEMA BAKKER WOUTER I ,  TULP MARTINUS TH M ,  SCHOFFELMEER ANTON N M ,  MARIE-ODILE CHRISTEN ,  MARYLENE CHOLLET ,  VAN VLIET BERNARD J

IPC: A61K20090101 ,  C07D20090101

Abstract: The present disclosure relates to dithiolethione derivatives as monoamino oxidase inhibitors, in particular MAO-B inhibitors, to methods for the preparation of these compounds and to novel intermediates useful for the synthesis of said dithiolethiones derivatives. The present disclosure also relates to the use of a compound disclosed herein for the manufacture of a medicament giving a beneficial effect. In embodiments of the present disclosure specific compounds disclosed herein are used for the manufacture of a medicament useful in the treatment, amelioration or prevention of conditions associated with dysfunction of monoamine neurotransmission. The compounds have the general formula (1) wherein the symbols have the meanings given in the specification.

公开(公告)号：AT285407T

公开(公告)日：2005-01-15

申请号：AT02784838

申请日：2002-07-03

Applicant: SOLVAY PHARM BV

Inventor： VAN MAARSEVEEN JAN H ,  VAN SCHARRENBURG GUSTAAF J M ,  TULP MARTINUS TH M ,  MCCREARY ANDREW C ,  IWEMA BAKKER WOUTER I ,  COOLEN HEIN K A C ,  HERREMANS ARNOLDUS H J ,  VAN DEN HOOGENBAND ADRIANUS

IPC: A61K31/495 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61P1/00 ,  A61P1/04 ,  A61P1/08 ,  A61P3/04 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P11/02 ,  A61P11/06 ,  A61P11/08 ,  A61P13/02 ,  A61P13/10 ,  A61P17/00 ,  A61P17/02 ,  A61P17/04 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P35/00 ,  A61P37/08 ,  A61P43/00 ,  C07D241/04 ,  C07D401/14 ,  C07D403/06 ,  C07D403/14 ,  C07D405/06 ,  C07D405/14 ,  C07D409/06 ,  C07D413/14 ,  C07D471/04 ,  C07D265/00 ,  C07D241/00 ,  C07D207/00

Abstract: The present invention relates to a group of novel piperazine oxime derivatives having interesting NK-1 antagonistic activity. The invention relates to compounds of the general formula (1) wherein: X represents phenyl or pyridyl substituted with 1 or 2 substituents from the group CH 3 , CF 3 , OCH 3 , halogen, cyano and 5-CF 3 -tetrazol-1-yl; Y represents 2- or 3-indolyl, phenyl, 7-aza-indol-3-yl or 3-indazolyl, 2-naphthyl, 3-benzo[b]thiophenyl, 2-benzofuranyl, which groups may be substituted with one or more halogen or alkyl (1-3C); n has the value 0-3; m has the value 0-2; R 1 represents NH 2 , NH-alkyl (1-3C), dialkyl (1-3C)N, morpholino or morpholino substituted with one or two methyl and/or methoxymethyl groups, thiomorpholino, 1,1-dioxothiomorpholino, 2-, 3- or 4-pyridyl or 4-CH 3 -piperazinyl; R 2 is hydrogen, alkyl (1-4C) or phenyl, or R 2 together with (CH 2 ) m wherein m is 1, and the intermediate carbon, nitrogen and oxygen atoms forms an isoxazolyl or a 4,5-dihydroisoxazolyl group; R 3 and R 4 independently represent hydrogen or methyl, or R 3 and R 4 together are oxygen. The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions comprising compounds with formula (1) as an active ingredient and the use of these compounds for the treatment of disorders in which neurokinin-1 receptors are involved

公开(公告)号：CA2446726A1

公开(公告)日：2003-01-23

申请号：CA2446726

申请日：2002-07-03

Applicant: SOLVAY PHARM BV

Inventor： MCCREARY ANDREW C ,  IWEMA BAKKER WOUTER I ,  HERREMANS ARNOLDUS H J ,  COOLEN HEIN K A C ,  VAN MAARSEVEEN JAN H ,  VAN DEN HOOGENBAND ADRIANUS ,  TULP MARTINUS TH M ,  VAN SCHARRENBURG GUSTAAF J M

IPC: A61K31/495 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61P1/00 ,  A61P1/04 ,  A61P1/08 ,  A61P3/04 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P11/02 ,  A61P11/06 ,  A61P11/08 ,  A61P13/02 ,  A61P13/10 ,  A61P17/00 ,  A61P17/02 ,  A61P17/04 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P35/00 ,  A61P37/08 ,  A61P43/00 ,  C07D241/04 ,  C07D401/14 ,  C07D403/06 ,  C07D403/14 ,  C07D405/06 ,  C07D405/14 ,  C07D409/06 ,  C07D413/14 ,  C07D471/04 ,  C07D207/00 ,  C07D241/00 ,  C07D265/00

Abstract: The present invention relates to a group of novel piperazine oxime derivativ es having interesting NK-1 antagonistic activity. The invention relates to compounds of the general formula (1) wherein:X represents phenyl or pyridyl substituted with 1 or 2 substituents from the group CH3, CF3, OCH3, halogen, cyano and 5-CF3-tetrazol-1-yl; Y represents 2- or 3-indolyl, phenyl, 7-aza- indol-3-yl or 3-indazolyl, 2-naphthyl, 3-benzo[b]thiophenyl, 2-benzofuranyl, which groups may be substituted with one or more halogen or alkyl (1-3C); n has the value 0-3; m has the value 0-2; R1 represents NH2, NH-alkyl (1-3C), dialkyl (1-3C)N, morpholino or morpholino substituted with one or two methyl and/or methoxymethyl groups, thiomorpholino, 1,1-dioxothiomorpholino, 2-, 3- or 4-pyridyl or 4-CH3-piperazinyl; R2 is hydrogen, alkyl (1-4C) or phenyl, o r R2 together with (CH2)m wherein m is 1, and the intermediate carbon, nitroge n and oxygen atoms forms an isoxazolyl or a 4,5-dihydroisoxazolyl group; R3 an d R4 independently represent hydrogen or methyl, or R3 and R4 together are oxygen. The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions comprising compounds wit h formula (1) as an active ingredient and the use of these compounds for the treatment of disorders in which neurokinin-1 receptors are involved.

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：DE602004022562D1

公开(公告)日：2009-09-24

申请号：DE602004022562

申请日：2004-09-23

Applicant: SOLVAY PHARM BV

Inventor： IWEMA BAKKER WOUTER I ,  VAN SCHARRENBURG GUSTAAF J M ,  VAN DEN HOOGENBAND ADRIANUS ,  MCCREARY ANDREW C

IPC: A61K31/4985 ,  A61P1/08 ,  A61P29/00 ,  C07D471/04

Abstract: The invention relates to hexahydro-pyrido[1,2-a]pyrazine derivatives having interesting neurokinin-NK1 receptor antagonistic activity. The invention also relates to methods for the preparation of these compounds, to pharmaceutical compositions containing a pharmacologically active amount of at least one of these compounds as an active ingredient, as well as to the use of these compositions for the treatment of disorders in which neurokinin receptors are involved. The invention relates to compounds represented by the general formula (1) wherein the symbols have the meanings as given in the description.

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：AR055862A1

公开(公告)日：2007-09-12

申请号：ARP060100616

申请日：2006-02-21

Applicant: SOLVAY PHARM BV

Inventor： DRUKARCH BENJAMIN ,  SCHOFFELMEER ANTON N M ,  FEENSTRA ROELOF W ,  CHRISTEN MARIE-ODILE ,  BURGOT JEAN-LOUIS ,  CHOLLET MARYLENE ,  IWEMA BAKKER WOUTER I ,  VAN VLIET BERNARD J ,  TULP MARTINUS TH M

IPC: C07D339/04 ,  A61K31/385

Abstract: La presente se refiere al uso de derivados de ditioltionas para preparar una composicion farmacéutica como inhibidores de la monoaminooxidasa, en particular inhibidores de MAO-B, a métodos para la reparacion de estos compuestos, a novedosos intermediarios utiles y composiciones farmacéuticas para la síntesis de dichos derivados de ditioltionas. La presente también se refiere al uso de un compuesto descripto aquí para la fabricacion de un medicamento que brinda un efecto beneficioso. En realizaciones de la presente se utilizan compuestos específicos descriptos para la fabricacion de un medicamento util en el tratamiento, mejora o prevencion de condiciones asociadas con disfuncion de la neurotransmision de monoaminas. Reivindicacion 1:Uso de un compuesto de la formula general (1) en donde: R1 y R2 son iguales o diferentes, y representan H, alquilo, alquenilo, alquinilo, arilo, F, Cl, Br, hidroxi, alquiloxi, alqueniloxi, ariloxi, aciloxi, amino, alquilamino, dialquilamino, arilamino, tio, alquiltio, ariltio, ciano, nitro, acilo, amido, alquilamido, dialquilamido, o R1 y R2 pueden formar junto con los átomos de C a los cuales están unidos un anillo aromático o no aromático de 5 o 6 miembros que contiene 0, 1, o 2 heteroátomos seleccionados de N, O o S, tales como anillos de furano, tiofeno, pirrol, oxazol, tiazol, imidazol, pirazol, isoxazol, isotiazol, 1,2,3-oxadiazol, 1,2,3-triazol, 1,3,4-tiadiazol, piridina, piridazina, pirimidina i pirazina; R1 y R2 pueden ellos mismos llevar sustituyentes adicionales seleccionados de H, alquilo, alquenilo, alquinilo, arilo, F, Cl, Br, hidroxilo, alquiloxi, aminoalquiloxi, morfolín-4-il-alcoxi, piperidin-1-il-alquiloxi, alqueniloxi, ariloxi, aciloxi, amino, alquilamino, dialquilamino, arilamino, tio, alquiltio, ariltio, ciano, oxo, nitro, acilo, amido, alquilamido o dialquilamido, y tautomeros, estereoisomeros y N-oxidos de los mismos, así como las sales, hidratos y solvatos farmacologicamente aceptables de dichos compuestos de la formula (1) y sus tautomeros, estereoisomeros y N-oxidos, para la preparacion de una composicion farmacéutica para el tratamiento, mejora, o prevencion de desordenes del estado de ánimo, desordenes bipolares I, desordenes bipolares II, desordenes depresivos unipolares, depresion menor, desorden afectivo estacional, depresion posnatal, distimia, depresion mayor, desordenes de ansiedad, desordenes de pánico, fobia social, desorden obsesivo compulsivo, desorden de estrés postraumático, desorden de ansiedad generalizada, desordenes relacionados con sustancias, desordenes de uso de sustancias, desordenes inducidos por sustancias, abstinencia de sustancias, déficit de atencion y desordenes de comportamiento disociador, desorden de hiperactividad con déficit de atencion, narcolepsia, desorden de control de impulsos, juego patologico, desordenes de alimentacion, anorexia nervosa, bulimia nervosa, desordenes de tics, desorden de Tourette, síndrome de piernas sin descanso, dolor, dolor de cabeza, dolor facial atípico, desorden de dolor y síndrome de dolor cronico, disfuncion sexual, obstruccion de las vías respiratorias, asma, desordenes de la motilidad gastrointestinal, hemorroides, espasmo del musculo liso en el tracto gastrointestinal y esfínteres, y disfuncion de la vejiga.