公开(公告)号：US5798350A

公开(公告)日：1998-08-25

申请号：US642264

申请日：1996-05-03

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 ,  A61K31/495 ,  A61K31/435 ,  C07D401/14 ,  C07D403/14

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; and E 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-; 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：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：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。

公开(公告)号：US5700445A

公开(公告)日：1997-12-23

申请号：US354905

申请日：1994-12-12

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.dbd., CH.sub.2 13 , and N.dbd.; 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 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X 1选自CH 2，NH，O和S; X2 + E，uns - + EE选自CH =，CH213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，如精神分裂症。

公开(公告)号：US5538965A

公开(公告)日：1996-07-23

申请号：US355297

申请日：1994-12-12

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 ,  C07D413/14 ,  C07D417/14

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-; R1表示C1-4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：US07291738B2

公开(公告)日：2007-11-06

申请号：US10375687

申请日：2003-02-27

Applicant: Jian-Min Fu

Inventor： Jian-Min Fu

IPC: C07D215/38

CPC classification number: C07D401/14 ,  C07D213/65 ,  C07D487/04

Abstract: The present invention provides compounds, for example, of formula (I): wherein R1, R2, and R3 have any of the values defined in the specification, as well as pharmaceutical compositions comprising the compounds. The invention also provides therapeutic methods, and processes and intermediates useful for preparing compounds of formula I.

Abstract translation: 本发明提供了化合物，例如式（I）化合物：其中R 1，R 2，R 3和R 3具有 本说明书中定义的值，以及包含该化合物的药物组合物。 本发明还提供了可用于制备式I化合物的治疗方法，方法和中间体。

公开(公告)号：US07074791B2

公开(公告)日：2006-07-11

申请号：US10682691

申请日：2003-10-09

Applicant: Jian-Min Fu

Inventor： Jian-Min Fu

IPC: C07D487/04 ,  A61K31/5025 ,  A61P25/22 ,  A61P25/24

CPC classification number: C07D487/04

Abstract: Disclosed are novel CRF receptor antagonists and their use as treatment of a variety of disorders, including disorders manifesting hypersecretion of CRF or associated with CRF or CRF receptors, such as anxiety, and depression. CRF receptor antagonists of the invention have the structure of formula (I): including stereoisomers or mixture of stereoisomers, pharmaceutically acceptable prodrugs, or pharmaceutically acceptable salts thereof, wherein in formula (I) R1 and R2 are independently selected from H, Me or OMe.

Abstract translation: 公开了新的CRF受体拮抗剂及其用于治疗多种疾病的用途，包括表现出CRF过度分泌或与CRF或CRF受体如焦虑和抑郁症相关的疾病。 本发明的CRF受体拮抗剂具有式（I）的结构：包括立体异构体或立体异构体的混合物，药学上可接受的前药或其药学上可接受的盐，其中在式（I）中R 1和R 2， SUP> 2 独立地选自H，Me或OMe。

公开(公告)号：US06992087B2

公开(公告)日：2006-01-31

申请号：US10298193

申请日：2002-11-15

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

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

IPC: A61K31/4965 ,  C07D241/00 ,  C07D241/02 ,  B65D75/80

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 1,4-pyrazine derivatives of 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1,4-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：US20060009459A1

公开(公告)日：2006-01-12

申请号：US11055034

申请日：2005-02-09

Applicant: Nagasree Chakka ,  Mikhail Chafeev ,  Sultan Chowdhury ,  Jian-Min Fu ,  Duanjie Hou ,  Rajender Kamboj ,  Vishnumurthy Kodumuru ,  Shifeng Liu ,  Vandna Raina ,  Shaoyi Sun ,  Serguei Sviridov ,  Michael Winther ,  Zaihui Zhang ,  Melwyn Abreo ,  Mark Holladay ,  Wenbao Li ,  Sengen Sun ,  Chi Tu ,  Heinz Gschwend

Inventor： Nagasree Chakka ,  Mikhail Chafeev ,  Sultan Chowdhury ,  Jian-Min Fu ,  Duanjie Hou ,  Rajender Kamboj ,  Vishnumurthy Kodumuru ,  Shifeng Liu ,  Vandna Raina ,  Shaoyi Sun ,  Serguei Sviridov ,  Michael Winther ,  Zaihui Zhang ,  Melwyn Abreo ,  Mark Holladay ,  Wenbao Li ,  Sengen Sun ,  Chi Tu ,  Heinz Gschwend

IPC: A61K31/501 ,  C07D403/02

CPC classification number: C07D237/20 ,  A61K31/00 ,  A61K31/501 ,  A61K31/551 ,  C07D237/22 ,  C07D237/24

Abstract: Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (Ia): where x, y, W, V, R2, R3, R4, R5, R6, R6a, R7, R7a, R8, R8a, R9 and R9a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

Abstract translation: 公开了治疗哺乳动物，优选人类的SCD介导的疾病或病症的方法，其中所述方法包括向有需要的哺乳动物施用式（Ia）化合物：其中x，y，W，V，R R 2，R 3，R 4，R 5，R 6，R 6，R 4， R 6a，R 7，R 7a，R 8，R 8a，R 8，R 7， 本文定义了9和9和9 9。 还公开了包含式（I）化合物的药物组合物。