公开(公告)号：US20090275618A1

公开(公告)日：2009-11-05

申请号：US12441570

申请日：2007-10-22

申请人： David Scott Coffey ,  Jingdan Hu ,  Stacy Jo Keding ,  Joseph Herman Krushinski, JR. ,  John Mehnert Schaus ,  David Edward Tupper

发明人： David Scott Coffey ,  Jingdan Hu ,  Stacy Jo Keding ,  Joseph Herman Krushinski, JR. ,  John Mehnert Schaus ,  David Edward Tupper

IPC分类号： A61K31/4439 ,  C07D401/12 ,  A61P25/18 ,  A61P25/30 ,  A61P3/04 ,  A61P25/28

CPC分类号： C07D401/12 ,  C07D207/38

摘要： Compounds and pharmaceutical compositions of Formula (I) by blockade of the CB1 receptors via an inverse agonism mechanism which are useful for reducing body weight in mammals, cognitive impairment associated with schizophrenia, mitigating treatment emergent weight gain observed during treatment with antipsychotics and have increased bioavailability.

摘要翻译： 式（I）的化合物和药物组合物通过反义激动机制阻断CB1受体，其可用于减少哺乳动物的体重，与精神分裂症相关的认知障碍，减轻用抗精神病药治疗期间观察到的治疗出现的体重增加并且具有增加的生物利用度 。

公开(公告)号：US08168659B2

公开(公告)日：2012-05-01

申请号：US12441570

申请日：2007-10-22

申请人： David Scott Coffey ,  Jingdan Hu ,  Stacy Jo Keding ,  Joseph Herman Krushinski, Jr. ,  John Mehnert Schaus ,  David Edward Tupper

发明人： David Scott Coffey ,  Jingdan Hu ,  Stacy Jo Keding ,  Joseph Herman Krushinski, Jr. ,  John Mehnert Schaus ,  David Edward Tupper

IPC分类号： A61K31/4439 ,  C07D401/12

CPC分类号： C07D401/12 ,  C07D207/38

摘要： Compounds and pharmaceutical compositions comprising compounds of the Formula as CB1 receptor inverse agonists useful for reducing body weight in mammals, treating cognitive impairment associated with schizophrenia, and mitigating treatment emergent weight gain observed during treatment with antipsychotics.

摘要翻译： 化合物和药物组合物，其包含式为CB1受体反向激动剂的化合物，其可用于减少哺乳动物体内的体重，治疗与精神分裂症相关的认知障碍，以及减轻在用抗精神病药治疗期间观察到的治疗急性体重增加。

公开(公告)号：US07214673B2

公开(公告)日：2007-05-08

申请号：US10505805

申请日：2003-03-17

申请人： Thomas Daniel Aicher ,  Zhaogen Chen ,  Joseph Herman Krushinski, Jr. ,  Yvan Le Huerou ,  Marta Maria Pineiro-Nunez ,  Kevin Michael Ruley ,  John Mehnert Schaus ,  Dennis Charles Thompson ,  David Edward Tupper ,  Ying Chen ,  Margaret Mary Faul ,  Vincent Patrick Rocco

发明人： Thomas Daniel Aicher ,  Zhaogen Chen ,  Joseph Herman Krushinski, Jr. ,  Yvan Le Huerou ,  Marta Maria Pineiro-Nunez ,  Kevin Michael Ruley ,  John Mehnert Schaus ,  Dennis Charles Thompson ,  David Edward Tupper ,  Ying Chen ,  Margaret Mary Faul ,  Vincent Patrick Rocco

IPC分类号： A61P25/00 ,  A61K31/55 ,  C07D243/10

CPC分类号： C07D487/04 ,  C07D243/38 ,  C07D495/04 ,  C07D513/04

摘要： Described herein are antipyschotic compounds of formula (I) wherein, A is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; Alk is (C1-4) alkylene optionally substituted with OH, methoxy, ethoxy, or F; Ar is optionally substituted phenyl, naphthyl, monocyclic heteroaromatic, or bicyclic heteroaromatic; R1 is hydrogen or (C1-4) alkyl optionally substituted with OH, OR3, or OCH2CH2OH, wherein R3 is (C1-2) alkyl; R2 is H, (C1-6) alkyl, halogen, fluorinated (C1-6) alkyl, OR4, SR4, NO2, CN, COR4, CONR5R6, SO2NR5R6, NR5R6, NR5COR4, NR5SO2R4, or optionally substituted phenyl, wherein R4 is hydrogen, (C1-6) alkyl, fluorinated (C1-6) alkyl, or optionally substituted phenyl, R5 and R6 are independently hydrogen, (C1-6) alkyl, or optionally substituted phenyl; Z is one or two substituents independently selected from hydrogen, halogen, (C1-6) alkyl, fluorinated (C1-6) alkyl, OR7, SR7, NO2, CN, COR7, CONR8R9, SO2NR8R9, NR8SO2R7, NR8R9, or optionally substituted phenyl, wherein R7 is hydrogen, (C1-6) alkyl, fluorinated alkyl, or optionally substituted phenyl, R8 and R9 are independently hydrogen, (C1-6) alkyl, or optionally substituted phenyl; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine D2 receptor and as agents for the treatment of psychosis and bipolar disorder, and pharmaceutical formulations of the compounds of formula (I).

公开(公告)号：US06777428B1

公开(公告)日：2004-08-17

申请号：US09890741

申请日：2001-12-04

申请人： Joseph Herman Krushinski, Jr. ,  Vincent Mancuso ,  Freddy Andre Napora ,  John Mehnert Schaus

发明人： Joseph Herman Krushinski, Jr. ,  Vincent Mancuso ,  Freddy Andre Napora ,  John Mehnert Schaus

IPC分类号： C07D21122

CPC分类号： C07D401/06 ,  C07D211/22 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12

摘要： The present invention relates to a compound of formula I and a process for making: or a pharmaceutical acid addition salt thereof; which are useful for activating 5-HT1F receptors and inhibiting neuronal protein extravasation in a mammal.

摘要翻译： 本发明涉及式I化合物及其制备方法：或其药用酸加成盐; 其可用于激活哺乳动物中的5-HT1F受体并抑制神经元蛋白质外渗。

公开(公告)号：US07230011B2

公开(公告)日：2007-06-12

申请号：US10466969

申请日：2002-01-17

申请人： Sandra Ann Filla ,  Michael Edward Flaugh ,  James Ronald Gillig ,  Lawrence Joseph Heinz ,  Joseph Herman Krushinski, Jr. ,  Bin Liu ,  Marta Maria Pineiro-Nunez ,  John Mehnert Schaus ,  John Stanley Ward

发明人： Sandra Ann Filla ,  Michael Edward Flaugh ,  James Ronald Gillig ,  Lawrence Joseph Heinz ,  Joseph Herman Krushinski, Jr. ,  Bin Liu ,  Marta Maria Pineiro-Nunez ,  John Mehnert Schaus ,  John Stanley Ward

IPC分类号： A61K31/454 ,  A61K31/4545 ,  C07D401/04 ,  C07D401/14

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D487/04

摘要： The present invention relates to compounds of formula I: which are antagonists of 5-HT6 receptor.

摘要翻译： 本发明涉及式I化合物，它是5-HT 6受体的拮抗剂。

公开(公告)号：US5962474A

公开(公告)日：1999-10-05

申请号：US977526

申请日：1997-11-24

申请人： James Edmund Audia ,  Bruce Anthony Dressman ,  James Joseph Droste ,  James Erwin Fritz ,  Stephen Warren Kaldor ,  Daniel James Koch ,  Joseph Herman Krushinski, Jr. ,  Jeffrey Scott Nissen ,  Vincent Patrick Rocco ,  John Mehnert Schaus ,  Dennis Charles Thompson

发明人： James Edmund Audia ,  Bruce Anthony Dressman ,  James Joseph Droste ,  James Erwin Fritz ,  Stephen Warren Kaldor ,  Daniel James Koch ,  Joseph Herman Krushinski, Jr. ,  Jeffrey Scott Nissen ,  Vincent Patrick Rocco ,  John Mehnert Schaus ,  Dennis Charles Thompson

IPC分类号： A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/47 ,  A61K31/495 ,  A61K31/535 ,  A61K31/54 ,  A61P25/00 ,  A61P43/00 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D407/14 ,  C07D409/14 ,  C07D417/14 ,  A61K31/40

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D407/14 ,  C07D409/14 ,  Y02P20/582

摘要： This invention provides novel 5-HT.sub.1F agonists of Formula I ##STR1## where A--B, R,R.sup.1 and X are as defined in the specification, which are useful for the treatment of migraine and associated disorders.

摘要翻译： 本发明提供式I的新型5-HT1F激动剂，其中A-B，R，R 1和X如说明书中所定义，其可用于治疗偏头痛及相关疾病。

公开(公告)号：US6133290A

公开(公告)日：2000-10-17

申请号：US334157

申请日：1999-06-16

申请人： Joseph Herman Krushinski, Jr. ,  John Mehnert Schaus

发明人： Joseph Herman Krushinski, Jr. ,  John Mehnert Schaus

IPC分类号： C07D401/04 ,  C07D455/02 ,  C07D471/04 ,  A61K31/454

CPC分类号： C07D455/02 ,  C07D401/04 ,  C07D471/04

摘要： The present invention relates to a compound of formula I: ##STR1## or a pharmaceutical acid addition salt thereof; which are useful for activating 5-HT.sub.1F receptors and inhibiting neuronal protein extravasation in a mammal.

摘要翻译： 本发明涉及式I化合物或其药用酸加成盐; 其可用于激活哺乳动物中的5-HT1F受体并抑制神经元蛋白质外渗。

公开(公告)号：US5708008A

公开(公告)日：1998-01-13

申请号：US619783

申请日：1996-03-20

申请人： James Edmund Audia ,  Bruce Anthony Dressman ,  James Joseph Droste ,  James Erwin Fritz ,  Stephen Warren Kaldor ,  Daniel James Koch ,  Joseph Herman Krushinski, Jr. ,  Jeffrey Scott Nissen ,  Vincent Patrick Rocco ,  John Mehnert Schaus ,  Dennis Charles Thompson

发明人： James Edmund Audia ,  Bruce Anthony Dressman ,  James Joseph Droste ,  James Erwin Fritz ,  Stephen Warren Kaldor ,  Daniel James Koch ,  Joseph Herman Krushinski, Jr. ,  Jeffrey Scott Nissen ,  Vincent Patrick Rocco ,  John Mehnert Schaus ,  Dennis Charles Thompson

IPC分类号： A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/47 ,  A61K31/495 ,  A61K31/535 ,  A61K31/54 ,  A61P25/00 ,  A61P43/00 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D407/14 ,  C07D409/14 ,  C07D417/14

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D407/14 ,  C07D409/14 ,  Y02P20/582

摘要： This invention provides novel 5-HT.sub.1F agonists of Formula I ##STR1## where A--B, R, R.sup.1 and X are as defined in the specification, which are useful for the treatment of migraine and associated disorders.

摘要翻译： 本发明提供式I的新型5-HT1F激动剂，其中A-B，R，R 1和X如说明书中所定义，其可用于治疗偏头痛及相关疾病。

公开(公告)号：US07384934B2

公开(公告)日：2008-06-10

申请号：US10523147

申请日：2003-07-28

申请人： Thomas Daniel Aicher ,  Zhaogen Chen ,  Yvan LeHuerou ,  Fionna Mitchell Martin ,  Marta Maria Pineiro-Nunez ,  Vincent Patrick Rocco ,  Kevin Michael Ruley ,  John Mehnert Schaus ,  Patrick Gianpietro Spinazze ,  David Edward Tupper

发明人： Thomas Daniel Aicher ,  Zhaogen Chen ,  Yvan LeHuerou ,  Fionna Mitchell Martin ,  Marta Maria Pineiro-Nunez ,  Vincent Patrick Rocco ,  Kevin Michael Ruley ,  John Mehnert Schaus ,  Patrick Gianpietro Spinazze ,  David Edward Tupper

IPC分类号： C07D403/04 ,  C07D495/04 ,  C07D513/04 ,  A61K31/55 ,  A61P25/18

CPC分类号： C07D403/04 ,  C07D495/04 ,  C07D513/04

摘要： Described herein are compounds of formula (I) wherein: is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, S, and O; Alk is (C1-4) alkylene or hydroxy substituted (C1-4) alkylene; X is oxygen or sulfur; R1 is hydrogen, (C1-6) fluroalkyl, (C3-6) cycloalkyl, or (C1-4) alkyl, wherein the (C1-4) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH2CH2OH, or —CN; R2 is H, halogen, (C1-6) fluoroalkyl, (C1-6) cycloalkyl, OR4, SR4, NO2, CN, COR4, C(O)OR4, CONR5R6, NR5R6, SO2NR5R6, NR5COR4, NR5SO2R4, optionally substituted aromatic, or (C1-6) alkyl, wherein (C1-6) alkyl is unsubstituted or substituted with a hydroxy group; R3 is hydrogen (C1-6) fluoroalkyl, (C2-6) alkenyl, Ar, (C1-4)alkyl-Ar, or (C1-4) alkyl wherein (C1-4) alkyly is unsubstituted or substituted with a phenyl; R4 is hydrogen, (C1-6) alkyl, (C1-6) fluoroalkyl, or optionally substituted aromatic; R5 and R6 are independently hydrogen, (C1-6) alkyl, or optionally substituted aromatic, R7 is hydrogen, (C1-6) alkyl, (C1-6) fluoroalkyl, or optionally substituted aromatic; R8 and R9 are independently hydrogen, (C1-6) alkyl, or optionally substituted aromatic; Ar is optionally substituted phenyl, napthyl, monocyclic heteroaromatic or bicyclic heteroaromatic; Z1 and Z2 are independently selected from hydrogen, halogen, (C1-6) alkyl, (C1-6) fluoroalkyl, OR7, SR7, NO2, CN, COR7, CONR8R9, NR8R9, and optionally substituted aromatic; and all salts, solvates, optical and geometric isomers, and crystalline forms thereof. Also, described are the use of the compounds of formula (I) as antagonists of the dopamine D2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I)

公开(公告)号：US5874427A

公开(公告)日：1999-02-23

申请号：US59768

申请日：1998-04-14

申请人： Sandra A. Filla ,  Joseph H. Krushinski, Jr. ,  John Mehnert Schaus

发明人： Sandra A. Filla ,  Joseph H. Krushinski, Jr. ,  John Mehnert Schaus

IPC分类号： A61P25/04 ,  A61K31/437 ,  A61K31/4375 ,  A61K31/55 ,  A61P25/06 ,  A61P43/00 ,  C07D455/02 ,  C07D455/03 ,  C07D471/04 ,  C07D519/00 ,  A61K31/435

CPC分类号： C07D455/00 ,  C07D471/04

摘要： This invention provides novel 5-HT.sub.1F agonists of the Formula ##STR1## in which X, Y, E, R, A, B, and n are as defined in the specification, which are useful for the treatment of migraine and associated disorders.

摘要翻译： 本发明提供了本发明的新颖的5-HT1F激动剂，其中X，Y，E，R，A，B和n如说明书中所定义，其可用于治疗偏头痛及相关疾病。