公开(公告)号：US09487462B2

公开(公告)日：2016-11-08

申请号：US13990684

申请日：2011-12-19

申请人： Péter Ferdinandy ,  Tamás Bálint Csont ,  Csaba Csonka ,  Krisztina Kedvesné Kupai ,  László Kovács ,  Attila Kis-Tamás ,  Ferenc Tamás Takács ,  Dénes Kónya ,  Gábor Medgyes ,  Sándor Cseh ,  István Hajdú ,  Zsolt Lörincz ,  György Dormán ,  Anikó Görbe

发明人： Péter Ferdinandy ,  Tamás Bálint Csont ,  Csaba Csonka ,  Krisztina Kedvesné Kupai ,  László Kovács ,  Attila Kis-Tamás ,  Ferenc Tamás Takács ,  Dénes Kónya ,  Gábor Medgyes ,  Sándor Cseh ,  István Hajdú ,  Zsolt Lörincz ,  György Dormán ,  Anikó Görbe

IPC分类号： A61K31/4025 ,  A61K31/417 ,  C07C47/575 ,  C07D213/30 ,  C07D233/64 ,  C07D233/90 ,  C07D277/28 ,  C07D277/56 ,  C07D401/12 ,  C07D417/12 ,  C07D417/14 ,  C07D213/38 ,  C07D277/30 ,  C07D295/16

CPC分类号： C07C47/575 ,  C07D213/30 ,  C07D213/38 ,  C07D233/64 ,  C07D233/90 ,  C07D277/28 ,  C07D277/30 ,  C07D277/56 ,  C07D295/16 ,  C07D401/12 ,  C07D417/12 ,  C07D417/14

摘要： Compounds of general formula (I), salts or solvates thereof and pharmaceutical compositions containing same: wherein Z is N or CH or the Z(R1) part is replaced with a covalent bond, m and n is 0, 1, 2 or 3; HET is heteroaryl; X is CF3, halogen, CO-heterocyclyl, COOR3 or CONHR3; R1 is H, (CH2)o-aryl, (CH2)p-heteroaryl, (CH2)q-biphenyl; C(O)—R5; S(O)2—R6; R2 is H, aryl, heteroaryl, Y—(CH2)r-aryl, Y—(CH2)s-heteroaryl, where some of the above substituents may be substituted; Y is O or S; with the exclusion of the compound where HET is 1,3-thiazol, X is COOH, R1 is 4-fluorophenyl and R2 is benzyloxy. The invention also relates to the use of a compound of general formula (I), salts or solvates thereof for the use in the prevention or treatment of diseases where the activation of MMPs is involved in the pathomechanism. In this aspect the use of the above excluded compound is also inventive.

公开(公告)号：US20130303572A1

公开(公告)日：2013-11-14

申请号：US13990684

申请日：2011-12-19

申请人： Péter Ferdinandy ,  Tamás Bálint Csont ,  Csaba Csonka ,  Krisztina Kedvesné Kupai ,  László Kovács ,  Attila Kis-Tamás ,  Ferenc Tamás Takács ,  Dénes Kónya ,  Gábor Medgyes ,  Sándor Cseh ,  István Hajdú ,  Zsolt Lõrincz ,  György Dormán ,  Anikó Görbe

发明人： Péter Ferdinandy ,  Tamás Bálint Csont ,  Csaba Csonka ,  Krisztina Kedvesné Kupai ,  László Kovács ,  Attila Kis-Tamás ,  Ferenc Tamás Takács ,  Dénes Kónya ,  Gábor Medgyes ,  Sándor Cseh ,  István Hajdú ,  Zsolt Lõrincz ,  György Dormán ,  Anikó Görbe

IPC分类号： C07D417/14 ,  C07D213/38 ,  C07D213/30 ,  C07C47/575 ,  C07D295/16 ,  C07D233/90 ,  C07D233/64 ,  C07D417/12 ,  C07D277/30

CPC分类号： C07C47/575 ,  C07D213/30 ,  C07D213/38 ,  C07D233/64 ,  C07D233/90 ,  C07D277/28 ,  C07D277/30 ,  C07D277/56 ,  C07D295/16 ,  C07D401/12 ,  C07D417/12 ,  C07D417/14

摘要： Compounds of general formula (I), salts or solvates thereof and pharmaceutical compositions containing same: wherein Z is N or CH or the Z(R1) part is replaced with a covalent bond, m and n is 0, 1, 2 or 3; HET is heteroaryl; X is CF3, halogen, CO-heterocyclyl, COOR3 or CONHR3; R1 is H, (CH2)o-aryl, (CH2)p-heteroaryl, (CH2)q-biphenyl; C(O)—R5; S(O)2—R6; R2 is H, aryl, heteroaryl, Y—(CH2)r-aryl, Y—(CH2)s-heteroaryl, where some of the above substituents may be substituted; Y is O or S; with the exclusion of the compound where HET is 1,3-thiazol, X is COOH, R1 is 4-fluorophenyl and R2 is benzyloxy. The invention also relates to the use of a compound of general formula (I), salts or solvates thereof for the use in the prevention or treatment of diseases where the activation of MMPs is involved in the pathomechanism. In this aspect the use of the above excluded compound is also inventive.

摘要翻译： 通式（I）的化合物，其盐或溶剂化物和含有它们的药物组合物：其中Z是N或CH或Z（R1）部分被共价键取代，m和n是0,1,2或3; HET是杂芳基; X是CF 3，卤素，CO-杂环基，COOR 3或CONHR 3; R1是H，（CH2）O-芳基，（CH2）p-杂芳基，（CH2）q-联苯基; C（O）-R 5; S（O）2 -R 6; R2是H，芳基，杂芳基，Y-（CH2）r-芳基，Y-（CH2）s-杂芳基，其中一些上述取代基可以被取代; Y为O或S; 除去HET是1,3-噻唑的化合物，X是COOH，R 1是4-氟苯基，R 2是苄氧基。 本发明还涉及通式（I）的化合物，其盐或溶剂合物用于预防或治疗MMPs的活化参与病理机制的疾病的用途。 在这方面，使用上述排除的化合物也是有创造性的。

公开(公告)号：US08278327B2

公开(公告)日：2012-10-02

申请号：US12848766

申请日：2010-08-02

申请人： John E. Bergmann ,  Neil S. Cutshall ,  Rene Onrust ,  Hongkui Zeng ,  Jennifer Lynn Gage ,  Derek Johnston ,  Sándor Cseh ,  László Ürögdi ,  Ákos Papp

发明人： John E. Bergmann ,  Neil S. Cutshall ,  Rene Onrust ,  Hongkui Zeng ,  Jennifer Lynn Gage ,  Derek Johnston ,  Sándor Cseh ,  László Ürögdi ,  Ákos Papp

IPC分类号： A01N43/42 ,  A61K31/47 ,  C07D215/00

CPC分类号： A61K31/341 ,  A61K31/404 ,  A61K31/4184 ,  A61K31/4409 ,  A61K31/47 ,  A61K31/4965 ,  A61K31/5415 ,  C07D209/18 ,  C07D213/81 ,  C07D215/36 ,  C07D235/16 ,  C07D235/28 ,  C07D249/18 ,  C07D279/16 ,  C07D333/24 ,  C07D405/12

摘要： Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. The compounds have the general structure: wherein m, n, p, x, R, R1, R2, R3, R4, R5, A and B, are defined herein, including pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.

摘要翻译： 公开了抑制PDE10的化合物，其可用于治疗各种病症，包括（但不限于）精神病性，焦虑症，运动障碍和/或神经障碍，例如帕金森病，亨廷顿氏病，阿尔茨海默病，脑炎，恐惧症 癫痫，失语症，贝尔麻痹，脑性麻痹，睡眠障碍，疼痛，图雷特综合征，精神分裂症，妄想症，药物诱发的精神病，恐慌和强迫症。 该化合物具有以下通式：其中m，n，p，x，R，R 1，R 2，R 3，R 4，R 5，A和B在本文中定义，包括其药学上可接受的盐，立体异构体，溶剂合物或前药。 还公开了含有本发明化合物与药学上可接受的载体的组合物的组合物，以及涉及其在需要其的温血动物中用于抑制PDE10的方法。

公开(公告)号：US07786139B2

公开(公告)日：2010-08-31

申请号：US12124051

申请日：2008-05-20

申请人： John E. Bergmann ,  Neil S. Cutshall ,  Rene Onrust ,  Hongkui Zeng ,  Jennifer Lynn Gage ,  Derek Johnston ,  Sándor Cseh ,  László Ürögdi ,  Ákos Papp

发明人： John E. Bergmann ,  Neil S. Cutshall ,  Rene Onrust ,  Hongkui Zeng ,  Jennifer Lynn Gage ,  Derek Johnston ,  Sándor Cseh ,  László Ürögdi ,  Ákos Papp

IPC分类号： A01N43/42 ,  A61K31/47 ,  C07D215/00

CPC分类号： A61K31/341 ,  A61K31/404 ,  A61K31/4184 ,  A61K31/4409 ,  A61K31/47 ,  A61K31/4965 ,  A61K31/5415 ,  C07D209/18 ,  C07D213/81 ,  C07D215/36 ,  C07D235/16 ,  C07D235/28 ,  C07D249/18 ,  C07D279/16 ,  C07D333/24 ,  C07D405/12

摘要： Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. The compounds have the general structure: wherein m, n, p, x, R, R1, R2, R3, R4, R5, A and B, are defined herein, including pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.

摘要翻译： 公开了抑制PDE10的化合物，其可用于治疗各种病症，包括（但不限于）精神病性，焦虑症，运动障碍和/或神经障碍，例如帕金森病，亨廷顿氏病，阿尔茨海默病，脑炎，恐惧症 癫痫，失语症，贝尔麻痹，脑性麻痹，睡眠障碍，疼痛，图雷特综合征，精神分裂症，妄想症，药物诱发的精神病，恐慌和强迫症。 该化合物具有以下通式：其中m，n，p，x，R，R 1，R 2，R 3，R 4，R 5，A和B在本文中定义，包括其药学上可接受的盐，立体异构体，溶剂合物或前药。 还公开了含有本发明化合物与药学上可接受的载体的组合物的组合物，以及涉及其在需要其的温血动物中用于抑制PDE10的方法。

公开(公告)号：US20110021509A1

公开(公告)日：2011-01-27

申请号：US12848766

申请日：2010-08-02

申请人： John E. Bergmann ,  Neil S. Cutshall ,  Rene Onrust ,  Hongkui Zeng ,  Jennifer Lynn Gage ,  Derek Johnston ,  Sándor Cseh ,  László Ürögdi ,  Ákos Papp

发明人： John E. Bergmann ,  Neil S. Cutshall ,  Rene Onrust ,  Hongkui Zeng ,  Jennifer Lynn Gage ,  Derek Johnston ,  Sándor Cseh ,  László Ürögdi ,  Ákos Papp

IPC分类号： A61K31/5415

CPC分类号： A61K31/341 ,  A61K31/404 ,  A61K31/4184 ,  A61K31/4409 ,  A61K31/47 ,  A61K31/4965 ,  A61K31/5415 ,  C07D209/18 ,  C07D213/81 ,  C07D215/36 ,  C07D235/16 ,  C07D235/28 ,  C07D249/18 ,  C07D279/16 ,  C07D333/24 ,  C07D405/12

摘要： Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. The compounds have the general structure: wherein m, n, p, x, R, R1, R2, R3, R4, R5, A and B, are defined herein, including pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.

摘要翻译： 公开了抑制PDE10的化合物，其可用于治疗各种病症，包括（但不限于）精神病性，焦虑症，运动障碍和/或神经障碍，例如帕金森病，亨廷顿氏病，阿尔茨海默病，脑炎，恐惧症 癫痫，失语症，贝尔麻痹，脑性麻痹，睡眠障碍，疼痛，图雷特综合征，精神分裂症，妄想症，药物诱发的精神病，恐慌和强迫症。 该化合物具有以下通式：其中m，n，p，x，R，R 1，R 2，R 3，R 4，R 5，A和B在本文中定义，包括其药学上可接受的盐，立体异构体，溶剂合物或前药。 还公开了含有本发明化合物与药学上可接受的载体的组合物的组合物，以及涉及其在需要其的温血动物中用于抑制PDE10的方法。