公开(公告)号：US07087617B2

公开(公告)日：2006-08-08

申请号：US10839055

申请日：2004-05-05

Applicant: Jeffrey W. Corbett ,  Michael Dalton Ennis ,  Kristine E. Frank ,  Jian-Min Fu ,  Robert Louis Hoffman ,  Patrick R. Verhoest

Inventor： Jeffrey W. Corbett ,  Michael Dalton Ennis ,  Kristine E. Frank ,  Jian-Min Fu ,  Robert Louis Hoffman ,  Patrick R. Verhoest

IPC: A61K31/505 ,  C07D239/32

CPC classification number: C07D239/42 ,  C07D213/72

Abstract: This invention relates to compounds of Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, or a pharmaceutically acceptable salt of a prodrug thereof. The compounds interact with CRF1 receptors, including human CRF1 receptors. This invention also relates to methods of using the compounds of the invention to treat a disorder or condition, the treatment of which can be effected or facilitated by antagonizing a CRF receptor, such as CNS disorders or diseases, particularly anxiety-related disorders such as anxiety, and mood disorders such as major depression.

Abstract translation: 本发明涉及式I化合物，其立体异构体，其药学上可接受的盐，其前药或其前药的药学上可接受的盐。 这些化合物与CRF1受体（包括人CRF 1受体）相互作用。 本发明还涉及使用本发明化合物治疗病症或病症的方法，所述疾病或病症的治疗可以通过拮抗CRF受体如CNS疾病或疾病，特别是焦虑相关疾病例如焦虑来实现或促进 ，以及心理障碍如重度抑郁症。

公开(公告)号：US07041672B2

公开(公告)日：2006-05-09

申请号：US10844004

申请日：2004-05-12

Applicant: Patrick R. Verhoest ,  Jeffrey W. Corbett ,  Michael Dalton Ennis ,  Kristine E. Frank ,  Jian-Min Fu ,  Robert Louis Hoffman

Inventor： Patrick R. Verhoest ,  Jeffrey W. Corbett ,  Michael Dalton Ennis ,  Kristine E. Frank ,  Jian-Min Fu ,  Robert Louis Hoffman

IPC: A61K31/4965 ,  C07D401/00 ,  C07D403/00 ,  C07D405/00 ,  C07D409/00

CPC classification number: C07D241/18 ,  C07D241/20 ,  C07D241/26 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D491/04 ,  G01N33/74 ,  G01N2333/5751 ,  G01N2500/02 ,  Y10S206/828

Abstract: Substituted aryl pyrazine derivatives of the formula I as defined herein, and their use in treating anxiety disorders, depression and stress related disorders are disclosed.

Abstract translation: 公开了本文定义的式I的取代的芳基吡嗪衍生物及其在治疗焦虑症，抑郁症和应激相关疾病中的用途。

公开(公告)号：US06930105B2

公开(公告)日：2005-08-16

申请号：US10271349

申请日：2002-10-15

Applicant: Jian-Min Fu

Inventor： Jian-Min Fu

IPC: A61K31/5383 ,  A61K31/554 ,  A61K51/00 ,  A61P3/04 ,  A61P25/00 ,  A61P25/22 ,  A61P25/24 ,  C07D498/22 ,  C07D513/22 ,  C07D265/28

CPC classification number: C07D498/22 ,  C07D513/22

Abstract: The present invention provides compounds of Formula (I): wherein R1, R2, R3, R4, R5, and R6, have any of the values defined in the specification, as well as pharmaceutical compositions comprising the compounds. The invention also provides therapeutic methods as well as processes and intermediates useful for preparing compounds of Formula (I). The compounds are 5-HT ligands and are useful for treating diseases wherein modulation of 5-HT2C activity is desired.

Abstract translation: 本发明提供式（I）的化合物：其中R 1，R 2，R 3，R 4， >，R 5和R 6具有说明书中定义的任何值，以及包含该化合物的药物组合物。 本发明还提供治疗方法以及可用于制备式（I）化合物的方法和中间体。 该化合物是5-HT配体，并且可用于治疗需要调节5-HT 2C活性的疾病。

公开(公告)号：US20050101613A1

公开(公告)日：2005-05-12

申请号：US10839055

申请日：2004-05-05

Applicant: Jeffrey Corbett ,  Michael Ennis ,  Kristine Frank ,  Jian-Min Fu ,  Robert Hoffman ,  Patrick Verhoest

Inventor： Jeffrey Corbett ,  Michael Ennis ,  Kristine Frank ,  Jian-Min Fu ,  Robert Hoffman ,  Patrick Verhoest

IPC: C07D213/72 ,  C07D239/42 ,  A61K31/506 ,  A61K31/4439 ,  C07D43/02

CPC classification number: C07D239/42 ,  C07D213/72

Abstract: This invention relates to compounds of Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, or a pharmaceutically acceptable salt of a prodrug thereof. The compounds interact with CRF, receptors, including human CRF, receptors. This invention also relates to methods of using the compounds of the invention to treat a disorder or condition, the treatment of which can be effected or facilitated by antagonizing a CRF receptor, such as CNS disorders or diseases, particularly anxiety-related disorders such as anxiety, and mood disorders such as major depression.

Abstract translation: 本发明涉及式I化合物，其立体异构体，其药学上可接受的盐，其前药或其前药的药学上可接受的盐。 该化合物与CRF，受体（包括人类CRF）受体相互作用。 本发明还涉及使用本发明化合物治疗病症或病症的方法，所述疾病或病症的治疗可以通过拮抗CRF受体如CNS疾病或疾病，特别是焦虑相关疾病例如焦虑来实现或促进 ，以及心理障碍如重度抑郁症。

公开(公告)号：US06465495B1

公开(公告)日：2002-10-15

申请号：US09363877

申请日：1999-07-29

Applicant: Arlindo L. Castelhano ,  Jian-Min Fu

Inventor： Arlindo L. Castelhano ,  Jian-Min Fu

IPC: C07D21302

CPC classification number: C07D213/64 ,  A61K31/4412 ,  A61K31/675 ,  C07D409/04 ,  C07F9/58 ,  C07F9/59

Abstract: Novel pyridone mimetics are disclosed which are useful for the treatment of SH2 domain related diseases.

Abstract translation: 公开了可用于治疗SH2结构域相关疾病的新型吡啶酮模拟物。

公开(公告)号：US06103715A

公开(公告)日：2000-08-15

申请号：US139715

申请日：1998-08-25

Applicant: Ashok Tehim ,  Jian-Min Fu ,  Sumanas Rakhit

Inventor： Ashok Tehim ,  Jian-Min Fu ,  Sumanas Rakhit

IPC: A61K31/00 ,  A61K31/55 ,  A61P25/18 ,  A61P25/20 ,  C07D243/10 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D487/12 ,  C07D491/00

CPC classification number: C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

Abstract: Described herein are D4 receptor-selective compounds of the general formula: ##STR1## wherein: A and B are independently selected, optionally substituted, saturated or unsaturated 5- or 6-membered, homo- or heterocyclic rings;X.sub.1 is selected from CH.sub.2, O, NH, S, C.dbd.O, CH--OH, CH--N(C.sub.1-4 alkyl).sub.2, C.dbd.CHCl, C.dbd.CHCN, N--C.sub.1-4 alkyl, N-acetyl, SO.sub.2 and SO;X.sub.2 - - - is selected from N.dbd., CH.sub.2 --, CH.dbd., C(O)--, O--, and S--;R.sub.1 represents C.sub.1-4 alkyl;Y is selected from CH and N;n is 0, 1 or 2;q is 1 or 2;R.sub.2 is C.sub.1-6 alkyl optionally incorporating a heteroatom selected from N, O and S;D is cyclohexane or benzene; andE is a saturated or unsaturated 5- or 6-membered heterocycle incorporating 1, 2 or 3 heteroatoms selected from O, N, and S, wherein E is optionally substituted with 1 or 2 substituents selected from halogen, C.sub.1-4 alkyl and halogen-substituted C.sub.1-4 alkyl;and acid addition salts, solvates and hydrates thereof. Their use as ligands for dopamine receptor identification and in a drug screening program, and as pharmaceuticals to treat indications in which the D4 receptor is implicated, such as schizophrenia, is also described.

Abstract translation: 本文描述的是具有以下通式的D4受体选择性化合物：其中：A和B独立地选择，任选取代的饱和或不饱和的5-或6-元，均 - 或杂环; X 1选自CH 2，O，NH，S，C = O，CH-OH，CH-N（C 1-4烷基）2，C = CHCl，C = CHCN，N-C 1-4烷基，N-乙酰基， 所以; X2 - - - 选自N =，CH 2 - ，CH =，C（O） - ，O-和S-; R 1表示C 1-4烷基; Y选自CH和N; n为0,1或2; q为1或2; R2是任选地加入选自N，O和S的杂原子的C 1-6烷基; D是环己烷或苯; 并且E是掺杂有1,2或3个选自O，N和S的杂原子的饱和或不饱和的5-或6-元杂环，其中E任选被1或2个选自卤素，C 1-4烷基和卤素 - 取代的C 1-4烷基; 及其酸加成盐，溶剂化物和水合物。 还描述了它们作为多巴胺受体鉴定和药物筛选程序的配体的用途，以及用于治疗其中涉及D4受体的适应症的药物，例如精神分裂症。

公开(公告)号：US5968478A

公开(公告)日：1999-10-19

申请号：US948051

申请日：1997-10-09

Applicant: Jian-Min Fu ,  Sumanas Rakhit

Inventor： Jian-Min Fu ,  Sumanas Rakhit

IPC: C07D243/38 ,  C07D267/18 ,  C07D337/14 ,  A61K51/00 ,  A61M36/14

CPC classification number: C07D267/18 ,  C07D243/38 ,  C07D337/14

Abstract: Described herein are D4 receptor-selective compounds of the general formula: ##STR1## wherein X.sub.1 is selected from CH.sub.2, NH, O and S;X.sub.2 -- is selected from CH=, CH.sub.2 --, and N=;R.sub.1 to R.sub.8 are each independently selected from H, C.sub.1-4 alkyl, halo, cyano, nitro and halo-substituted C.sub.1-4 alkyland acid addition salts, solvates and hydrates thereof. Their use as ligands for dopamine receptor identification and in a drug screening program, and as pharmaceuticals to treat indications in which the D4 receptor is implicated, such as schizophrenia, is also described.

Abstract translation: 本文描述的是具有以下通式的D4受体选择性化合物：其中X 1选自CH 2，NH，O和S; X2-选自CH =，CH 2 - 和N =; R 1至R 8各自独立地选自H，C 1-4烷基，卤素，氰基，硝基和卤素取代的C 1-4烷基及其酸加成盐，溶剂合物和水合物。 还描述了它们作为多巴胺受体鉴定和药物筛选程序的配体的用途，以及用于治疗其中涉及D4受体的适应症的药物，例如精神分裂症。

公开(公告)号：US5814628A

公开(公告)日：1998-09-29

申请号：US762984

申请日：1996-12-10

Applicant: Jian-Min Fu ,  Ashok Tehim ,  Robert A. Kirby

Inventor： Jian-Min Fu ,  Ashok Tehim ,  Robert A. Kirby

IPC: C07D267/20 ,  C07D401/14 ,  A61K31/55 ,  C07D403/14

CPC classification number: C07D267/20

Abstract: Described herein are D4 receptor-selective compounds of the general formula: ##STR1## wherein: A and B are independently selected, optionally substituted, saturated or unsaturated 5- or 6-membered, homo- or heterocyclic rings; X.sub.1 is selected from CH.sub.2, O, NH, S, C.dbd.O, CH--OH, CH--N(C.sub.1-4 alkyl).sub.2, C.dbd.CHCI, C.dbd.CHCN, N--C.sub.1-4 alkyl, N-acetyl, SO.sub.2 and SO; X.sub.2 --is selected from N.dbd., CH.sub.2 --, CH.dbd., C(O)--, O--, and S--; Y is selected from CH and N; Z is cyano R.sub.1 represents C.sub.1-4 alkyl; m is 0, 1, 2 or 3; n is 0, 1 or 2; q is 1 or 2; and D is a 5, 6 or 7-membered, saturated or unsaturated, homo- or heterocyclic ring; and acid addition salts, solvates and hydrates thereof. Their use as ligands for dopamine receptor identification and in a drug screening program, and as pharmaceuticals to treat indications in which the D4 receptor is implicated, such as schizophrenia, is also described.

Abstract translation: 本文描述的是具有以下通式的D4受体选择性化合物：其中：A和B独立选择，任选取代的饱和或不饱和的5-或6-元，杂环或杂环; X 1选自CH 2，O，NH，S，C = O，CH-OH，CH-N（C 1-4烷基）2，C = CHCl，C = CHCN，N-C 1-4烷基，N-乙酰基， 所以; X2-选自N =，CH 2 - ，CH =，C（O） - ，O-和S-; Y选自CH和N; Z是氰基，R 1表示C 1-4烷基; m为0,1,2或3; n为0,1或2; q为1或2; 且D为5,6或7元饱和或不饱和的均聚或杂环; 及其酸加成盐，溶剂化物和水合物。 还描述了它们作为多巴胺受体鉴定和药物筛选程序的配体的用途，以及用于治疗其中涉及D4受体的适应症的药物，例如精神分裂症。

公开(公告)号：US5602124A

公开(公告)日：1997-02-11

申请号：US354765

申请日：1994-12-12

Applicant: Ashok Tehim ,  Jian-Min Fu ,  Sumanas Rakhit

Inventor： Ashok Tehim ,  Jian-Min Fu ,  Sumanas Rakhit

IPC: C07D243/38 ,  C07D267/20 ,  A61K31/55 ,  C07D403/04

CPC classification number: C07D243/38 ,  C07D267/20

Abstract: Described herein are 5-HT2 receptor-selective compounds of Formula I: ##STR1## wherein: A and B are independently selected, optionally substituted, saturated or unsaturated 5- or 6-membered, homo- or heterocyclic rings;X.sub.1 is selected from CH.sub.2, O, NH, S, C.dbd.O, CH--OH, CH--N(C.sub.1-4 alkyl).sub.2, C.dbd.CHCl, C.dbd.CHCN, N--C.sub.1-4 alkyl, N-acetyl, SO.sub.2 and SO;X.sub.2 - - - is selected from N.dbd., CH.sub.2 --, CH.dbd., C(O)--, O--, and S--;R.sub.1 is C.sub.1-6 alkyl optionally substituted with a substituent selected from OH, halo, C.sub.1-4 alkyl and C.sub.1-4 alkoxy; andR.sub.2, R.sub.3 and R.sub.4 are independently selected from H and R.sub.1 ;and acid addition salts, solvates and hydrates thereof. Their use as ligands for serotonin 5-HT2 receptor identification and in a drug screening program, and as pharmaceuticals to treat indications in which the 5-HT2 receptor is implicated, such as hypertension, thrombosis, migraine, vasospasm, ischemia, depression, anxiety, schizophrenia, sleep disorders and appetite disorders is also described.

Abstract translation: 本文描述的是式I的5-HT 2受体选择性化合物：其中：A和B独立地选择，任选取代的饱和或不饱和的5-或6-元，均 - 或杂环; X 1选自CH 2，O，NH，S，C = O，CH-OH，CH-N（C 1-4烷基）2，C = CHCl，C = CHCN，N-C 1-4烷基，N-乙酰基， 所以; X2 - - - 选自N =，CH 2 - ，CH =，C（O） - ，O-和S-; R1是任选被选自OH，卤素，C 1-4烷基和C 1-4烷氧基的取代基取代的C 1-6烷基; 并且R 2，R 3和R 4独立地选自H和R 1; 及其酸加成盐，溶剂化物和水合物。 它们用作5-羟色胺5-HT2受体鉴定和药物筛选程序的配体，以及用作治疗其中涉及5-HT2受体的适应症的药物，例如高血压，血栓形成，偏头痛，血管痉挛，局部缺血，抑郁，焦虑， 还描述了精神分裂症，睡眠障碍和食欲障碍。