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。