公开(公告)号：US6156751A

公开(公告)日：2000-12-05

申请号：US393789

申请日：1999-09-10

申请人： Alan Hutchison ,  Jun Yuan ,  Raymond F. Horvath

发明人： Alan Hutchison ,  Jun Yuan ,  Raymond F. Horvath

IPC分类号： C07D487/08 ,  A61K31/495 ,  C07D247/00

CPC分类号： C07D487/08

摘要： This invention encompasses compounds of the formula: ##STR1## where either R.sub.1 or R.sub.2 represents ##STR2## and the other represents hydrogen or straight or branched chain lower alkyl having 1-6 carbon atoms; andX is oxygen, methylene, or NH;Y is represents various inorganic and organic substituents;Z is hydrogen, amino or NHR.sub.6 where R.sub.6 is lowere alkyl having 1-6 carbon atoms;T is hydrogen, halogen, hydroxy, or lower alkoxy having 1-6 carbon atoms; andA is methylene, carbonyl or CHOH.These compounds are selective partial agonists or antagonists at brain monoamine receptor subtypes or prodrugs thereof and are useful in the diagnosis and treatment of affective disorders such as schizophrenia and depression as well as certain movement disorders such as Parkinsonism. Furthermore compounds of this invention may be useful in treating the extrapyramidal side effects associated with the use of conventional neurolepticagents. These compounds show unexpectedly atypical antipsychotic profiles (clozapine-like) in the animal models described in this patent.

摘要翻译： 本发明包括下式的化合物：其中R 1或R 2表示，另一个表示氢或具有1-6个碳原子的直链或支链低级烷基; X为氧，亚甲基或NH; Y代表各种无机和有机取代基; Z是氢，氨基或NHR 6，其中R6是具有1-6个碳原子的低级烷基; T是氢，卤素，羟基或具有1-6个碳原子的低级烷氧基; A是亚甲基，羰基或CHOH。 这些化合物是脑单胺受体亚型或其前药的选择性部分激动剂或拮抗剂，并且可用于诊断和治疗情感障碍如精神分裂症和抑郁症以及某些运动障碍如帕金森综合征。 此外，本发明的化合物可用于治疗与使用常规精神抑制剂相关的锥体束外副作用。 这些化合物在本专利描述的动物模型中显示出意想不到的非典型抗精神病药谱（氯氮平样）。

公开(公告)号：US5952501A

公开(公告)日：1999-09-14

申请号：US429060

申请日：1995-04-26

申请人： Alan Hutchison ,  Jun Yuan ,  Raymond F. Horvath

发明人： Alan Hutchison ,  Jun Yuan ,  Raymond F. Horvath

IPC分类号： C07D487/08 ,  C07D247/00 ,  A61K31/495

CPC分类号： C07D487/08

摘要： This invention encompasses compounds of the formula: where either R.sub.1 or R.sub.2 represents ##STR1## and the other represents hydrogen or straight or branched chain lower alkyl having 1-6 carbon atoms; andX is oxygen, methylene, or NH;Y is represents various inorganic and organinc substituents;Z is hydrogen, amino or NHR.sub.6 where R.sub.6 is lower alkyl having 1-6 carbon atoms;T is hydrogen, halogen, hydroxy, or lower alkoxy having 1-6 carbon atoms; andA is methylene, carbonyl or CHOH.These compounds are selective partial agonists or antagonists at brain monoamine receptor subtypes or prodrugs thereof and are useful in the diagnosis and treatment of affective disorders such as schizophrenia and depression as well as certain movement disorders such as Parkinsonism. Furthermore compounds of this invention may be useful in treating the extrapyramidal side effects associated with the use of conventional neuroleptic agents. These compounds show unexpectedly atypical antipsychotic profiles (clozapine-like) in the animal models described in this patent.

摘要翻译： 本发明包括下式的化合物：其中R 1或R 2表示，另一个表示氢或具有1-6个碳原子的直链或支链低级烷基; X为氧，亚甲基或NH; Y代表各种无机和有机取代基; Z是氢，氨基或NHR6，其中R6是具有1-6个碳原子的低级烷基; T是氢，卤素，羟基或具有1-6个碳原子的低级烷氧基; A是亚甲基，羰基或CHOH。 这些化合物是脑单胺受体亚型或其前药的选择性部分激动剂或拮抗剂，并且可用于诊断和治疗情感障碍如精神分裂症和抑郁症以及某些运动障碍如帕金森综合征。 此外，本发明的化合物可用于治疗与使用常规精神抑制剂相关的锥体束外副作用。 这些化合物在本专利描述的动物模型中显示出意想不到的非典型抗精神病药谱（氯氮平样）。

公开(公告)号：US06355651B1

公开(公告)日：2002-03-12

申请号：US09657634

申请日：2000-09-06

申请人： Raymond F. Horvath ,  Alan Hutchison

发明人： Raymond F. Horvath ,  Alan Hutchison

IPC分类号： A61K31437

CPC分类号： C07D471/04 ,  C07D471/14

摘要： Disclosed are compounds of the formula: wherein Ar is optionally substituted aryl or heteroaryl R1 is hydrogen or alkyl; R7 is hydrogen or alkyl; R2 is hydrogen, halogen, alkyl or alkoxy; or R1 and R2 taken together with the ring to which they are attached form a 5-9 membered saturated or aromatic ring optionally having a hetero atom selected from oxygen, sulfur or nitrogen; R3 and R4 are independently hydrogen, alkyl, cycloalkyl, aryl or heteroaryl groups; or R3 and R4 together with the nitrogen atom to which they are attached form a 5-8 membered ring; and R5 is hydrogen, halogen, straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy or thioalkoxy having 1-6 carbon atoms, which compounds are highly selective partial agonists or antagonists at human Corticotropin-Releasing Factor 1 (CRF1) receptors and are useful in the diagnosis and treatment of treating stress related disorders such as post trumatic stress disorder (PTSD) as well as depression, headache and anxiety.

摘要翻译： 公开了下式的化合物：其中Ar是任选取代的芳基或杂芳基R 1是氢或烷基; R 7是氢或烷基; R 2是氢，卤素，烷基或烷氧基; 或R 1和R 2与它们所连接的环一起形成任选具有选自氧，硫或氮的杂原子的5-9元饱和或芳环; R 3和R 4独立地为氢，烷基，环烷基，芳基或杂芳基 团体 或R 3和R 4与它们所连接的氮原子一起形成5-8元环; 和R 5是氢，卤素，具有1-6个碳原子的直链或支链低级烷基，或具有1-6个碳原子的直链或支链低级烷氧基或硫代烷氧基，该化合物是人促皮激素释放因子的高选择性部分激动剂或拮抗剂 1（CRF1）受体，可用于诊断和治疗应激相关疾病如后遗传性应激障碍（PTSD）以及抑郁，头痛和焦虑。

公开(公告)号：US06670371B2

公开(公告)日：2003-12-30

申请号：US10096239

申请日：2002-03-12

申请人： Raymond F. Horvath ,  Alan Hutchison

发明人： Raymond F. Horvath ,  Alan Hutchison

IPC分类号： A61K31437

CPC分类号： C07D471/04 ,  C07D471/14

摘要： Disclosed are compounds of the formula: wherein Ar is optionally substituted aryl or heteroaryl R1 is hydrogen or alkyl; R7 is hydrogen or alkyl; R2 is hydrogen, halogen, alkyl or alkoxy; or R1 and R2 taken together with the ring to which they are attached form a 5-9 membered saturated or aromatic ring optionally having a hetero atom selected from oxygen, sulfur or nitrogen; R3 and R4 are independently hydrogen, alkyl, cycloalkyl, aryl or heteroaryl groups; or R3 and R4 together with the nitrogen atom to which they are attached form a 5-8 membered ring; and R5 is hydrogen, halogen, straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy or thioalkoxy having 1-6 carbon atoms, which compounds are highly selective partial agonists or antagonists at human Corticotropin-Releasing Factor 1 (CRF1) receptors and are useful in the diagnosis and treatment of treating stress related disorders such as post trumatic stress disorder (PTSD) as well as depression, headache and anxiety.

摘要翻译： 公开了下式的化合物：其中Ar是任选取代的芳基或杂芳基R 1是氢或烷基; R 7是氢或烷基; R 2是氢，卤素，烷基或烷氧基; 或者R 1和R 2与它们所连接的环一起形成任选具有选自氧，硫或氮的杂原子的5-9元饱和或芳环; R 3和R 4独立地是氢，烷基，环烷基，芳基或杂芳基 团体 或R 3和R 4与它们所连接的氮原子一起形成5-8元环; 和R 5是氢，卤素，具有1-6个碳原子的直链或支链低级烷基，或具有1-6个碳原子的直链或支链低级烷氧基或硫代烷氧基，该化合物是人促皮激素释放因子的高选择性部分激动剂或拮抗剂 1（CRF1）受体，可用于诊断和治疗应激相关疾病如后遗传性应激障碍（PTSD）以及抑郁，头痛和焦虑。

公开(公告)号：US06281237B1

公开(公告)日：2001-08-28

申请号：US09540478

申请日：2000-03-31

申请人： Raymond F. Horvath ,  Ping Ge ,  Taeyoung Yoon ,  Alan Hutchison

发明人： Raymond F. Horvath ,  Ping Ge ,  Taeyoung Yoon ,  Alan Hutchison

IPC分类号： A61K314184

CPC分类号： C07D235/14 ,  C07D209/14 ,  G01N2333/726

摘要： Disclosed are compounds of the forumla: or the pharmaceutically acceptable non-toxic salts thereof wherein; A is N or CH; R1 and R2 represents hydrogen or lower alkyl; G, R3, R4, R5, R6, R7 and R8 are variables defined herein. These compounds are modulators of CRF receptors and are therefore useful for treating affective disorders, anxiety, depression, eating disorders, and stress disorders in humans and other animals. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided. Compounds of the invention are also useful as probes for the localization of CRF receptors and as standards in assays for CRF receptor binding. Methods of using the compounds in receptor localization studies are given.

摘要翻译： 公开了该论坛的化合物或其药学上可接受的无毒盐，其中：A是N或CH; R 1和R 2表示氢或低级烷基; G，R 3，R 4，R 5，R 6，R 7和R 8是本文定义的变量 这些化合物是CRF受体的调节剂，因此可用于治疗人类和其他动物中的情感障碍，焦虑症，抑郁症，进食障碍和应激障碍。 还提供了治疗这种病症以及包装的药物组合物的方法。本发明的化合物还可用作CRF受体定位的探针，并且作为用于CRF受体结合的测定中的标准物。 给出了在受体定位研究中使用化合物的方法。

公开(公告)号：US6133282A

公开(公告)日：2000-10-17

申请号：US368541

申请日：1999-08-05

申请人： Raymond F. Horvath ,  Alan Hutchison

发明人： Raymond F. Horvath ,  Alan Hutchison

IPC分类号： A61P25/24 ,  C07D471/04 ,  C07D471/14 ,  A61K31/437

CPC分类号： C07D471/04 ,  C07D471/14

摘要： Disclosed are compounds of the formula: ##STR1## wherein Ar is optionally substituted aryl or heteroarylR.sub.1 is hydrogen or alkyl;R.sub.7 is hydrogen or alkyl;R.sub.2 is hydrogen, halogen, alkyl or alkoxy; orR.sub.1 and R.sub.2 taken together with the ring to which they are attached form a 5-9 membered saturated or aromatic ring optionally having a hetero atom selected from oxygen, sulfur or nitrogen;R.sub.3 and R.sub.4 are independently hydrogen, alkyl, cycloalkyl, aryl or heteroaryl groups; orR.sub.3 and R.sub.4 together with the nitrogen atom to which they are attached form a 5-8 membered ring; andR.sub.5 is hydrogen, halogen, straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy or thioalkoxy having 1-6 carbon atoms,which compounds are highly selective partial agonists or antagonists at human Corticotropin-Releasing Factor 1 (CRF1) receptors and are useful in the diagnosis and treatment of treating stress related disorders such as post trumatic stress disorder (PTSD) as well as depression, headache and anxiety.

摘要翻译： 公开了下式的化合物：其中Ar是任选取代的芳基或杂芳基R 1是氢或烷基; R7是氢或烷基; R2是氢，卤素，烷基或烷氧基; 或者R 1和R 2与它们所连接的环一起形成任选具有选自氧，硫或氮的杂原子的5-9元饱和或芳环; R3和R4独立地是氢，烷基，环烷基，芳基或杂芳基; 或R 3和R 4与它们所连接的氮原子一起形成5-8元环; R5为氢，卤素，具有1-6个碳原子的直链或支链低级烷基，或具有1-6个碳原子的直链或支链低级烷氧基或硫代烷氧基，该化合物是人促皮素激素释放的高度选择性部分激动剂或拮抗剂 因子1（CRF1）受体，可用于诊断和治疗应激相关疾病，如创伤后应激障碍（PTSD）以及抑郁，头痛和焦虑。

公开(公告)号：US06583169B2

公开(公告)日：2003-06-24

申请号：US09928722

申请日：2001-08-13

申请人： Raymond F. Horvath ,  Ping Ge ,  Taeyoung Yoon ,  Alan Hutchison

发明人： Raymond F. Horvath ,  Ping Ge ,  Taeyoung Yoon ,  Alan Hutchison

IPC分类号： A61K31404

CPC分类号： C07D235/14 ,  C07D209/14 ,  G01N2333/726

摘要： Disclosed are compounds of the formula: or the pharmaceutically acceptable non-toxic salts thereof wherein; A is N or CH; R1 and R2 represents hydrogen or lower alkyl; G, R3, R4, R5, R6, R7 and R8 are variables defined herein. These compounds are modulators of CRF receptors and are therefore useful for treating affective disorders, anxiety, depression, eating disorders, and stress disorders in humans and other animals. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided. Compounds of the invention are also useful as probes for the localization of CRF receptors and as standards in assays for CRF receptor binding. Methods of using the compounds in receptor localization studies are given.

摘要翻译： 公开了下式的化合物或其药学上可接受的无毒盐，其中A是N或CH; R 1和R 2表示氢或低级烷基; G，R 3，R 4，R 5，R 6，R 7和R 8是本文定义的变量 这些化合物是CRF受体的调节剂，因此可用于治疗人类和其他动物中的情感障碍，焦虑症，抑郁症，进食障碍和应激障碍。 还提供了治疗这种病症以及包装的药物组合物的方法。本发明的化合物还可用作CRF受体定位的探针，并且作为用于CRF受体结合的测定中的标准物。 给出了在受体定位研究中使用化合物的方法。

公开(公告)号：US5955613A

公开(公告)日：1999-09-21

申请号：US542854

申请日：1995-10-13

申请人： Raymond F. Horvath ,  Alan Hutchison

发明人： Raymond F. Horvath ,  Alan Hutchison

IPC分类号： C07D471/04 ,  C07D471/14

CPC分类号： C07D471/04 ,  C07D471/14

摘要： Disclosed are compounds of the formula: ##STR1## wherein Ar is optionally substituted aryl or heteroarylR.sub.1 is hydrogen or alkyl;R.sub.7 is hydrogen or alkyl;R.sub.2 is hydrogen, halogen, alkyl or alkoxy; orR.sub.1 and R.sub.2 taken together with the ring to which they are attached form a 6 membered aromatic ring optionally having a nitrogen atom,R.sub.3 and R.sub.4 are independently hydrogen, alkyl, cycloalkyl, aryl or heteroaryl groups; or R.sub.3 and R.sub.4 together with the nitrogen atom to which they are attached form a 5-8 membered ring; andR.sub.5 is hydrogen, halogen, straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy or thioalkoxy having 1-6 carbon atoms,which compounds are highly selective partial agonists or antagonists at human Corticotropin-Releasing Factor 1 (CRF1) receptors and are useful in the diagnosis and treatment of treating stress related disorders such as post trumatic stress disorder (PTSD) as well as depression, headache and anxiety.

摘要翻译： 公开了下式的化合物：其中Ar是任选取代的芳基或杂芳基R 1是氢或烷基; R7是氢或烷基; R2是氢，卤素，烷基或烷氧基; 或者R 1和R 2与它们所连接的环一起形成任选具有氮原子的6元芳环，R 3和R 4独立地是氢，烷基，环烷基，芳基或杂芳基; 或R 3和R 4与它们所连接的氮原子一起形成5-8元环; R5为氢，卤素，具有1-6个碳原子的直链或支链低级烷基，或具有1-6个碳原子的直链或支链低级烷氧基或硫代烷氧基，该化合物是人促皮素激素释放的高度选择性部分激动剂或拮抗剂 因子1（CRF1）受体，可用于诊断和治疗应激相关疾病，如创伤后应激障碍（PTSD）以及抑郁，头痛和焦虑。

公开(公告)号：US20060142324A1

公开(公告)日：2006-06-29

申请号：US11355439

申请日：2006-02-15

申请人： Jun Yuan ,  George Maynard ,  Alan Hutchison

发明人： Jun Yuan ,  George Maynard ,  Alan Hutchison

IPC分类号： A61K31/4745 ,  C07D471/02

CPC分类号： C07D471/04 ,  C07D495/04

摘要： Disclosed are compounds of formula (I) or pharmaceutically acceptable non-toxic salts or pharmaceutically acceptable solvates thereof wherein: (II) represents (a), (b), (c) or (d) and W, X, Y, A, B, C, D, E are variables as described herein. These compounds are highly selective agonists or antagonists at NK3 receptors or prodrugs thereof. The novel tachykinin NK-3 receptor antagonists contained in this invention have potential utility in the treatment of a broad array of disorders and diseases of the central nervous system (CNS) and periphery in mammals in which activation of NK-3 receptors is of importance.

公开(公告)号：US06559163B2

公开(公告)日：2003-05-06

申请号：US09931549

申请日：2001-08-16

申请人： Guolin Cai ,  Jun Yuan ,  Kevin Currie ,  Pamela Albaugh ,  Alan Hutchison

发明人： Guolin Cai ,  Jun Yuan ,  Kevin Currie ,  Pamela Albaugh ,  Alan Hutchison

IPC分类号： A61K314709

CPC分类号： C07D231/12 ,  C07D215/52 ,  C07D233/56 ,  C07D249/08 ,  C07D401/06 ,  C07D401/14 ,  C07D409/04

摘要： Disclosed are compounds of the formula or pharmaceutically acceptable salts thereof wherein: represents: and A, B, G, D, E, Ra, Rb, W, and Z are defined herein. These compounds are agonists, antagonists or inverse agonists for GABAA brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAA brain receptors and are therefore useful in the diagnosis and treatment of anxiety, depression, Down Syndrome, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory. Pharmaceutical compositions, including packaged pharmaceutical compositions, are further provided. Compounds of the invention are also useful as probes for the localization of GABAA receptors in tissue samples.

摘要翻译： 公开了式或其药学上可接受的盐的化合物，其中：表示：并且A，B，G，D，E，Ra，Rb，W和Z在本文中定义。 这些化合物是GABAA脑受体的激动剂，拮抗剂或反向激动剂或GABAA脑受体的激动剂，拮抗剂或反向激动剂的前药，因此可用于诊断和治疗焦虑症，抑郁症，唐氏综合征，睡眠和癫痫发作，过量与 苯二氮卓类药物和增强记忆力。 还提供药物组合物，包括包装的药物组合物。 本发明的化合物也可用作组织样品中GABA A受体定位的探针。