公开(公告)号：US06353109B2

公开(公告)日：2002-03-05

申请号：US09088522

申请日：1998-06-01

申请人： Pamela Albaugh ,  Gang Liu ,  Alan Hutchison

发明人： Pamela Albaugh ,  Gang Liu ,  Alan Hutchison

IPC分类号： C07C23359

CPC分类号： C07D401/12 ,  C07D209/42 ,  C07D409/12 ,  C07D471/04

摘要： Disclosed are compounds of the formula or the pharmaceutically acceptable non-toxic salts thereof wherein: W represents substituted or unsubstituted aryl or heteroaryl; T is hydrogen, halogen, hydroxyl, amino or alkyl; X is hydrogen, hydroxy, or lower alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and R3 and R4 represent substituted or unsubstituted organic residues. These compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAa brain receptors. These compounds are useful in the diagnosis and treatment of anxiety, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory.

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：W表示取代或未取代的芳基或杂芳基; T是氢，卤素，羟基，氨基或烷基; X是氢，羟基或低级烷基; m是0 ，1或2; n为0,1或2; R 3和R 4代表取代或未取代的有机残基。这些化合物是GABAa脑受体的高选择性激动剂，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。 这些化合物可用于诊断和治疗焦虑，睡眠和癫痫发作，用苯二氮卓类药物过量并用于记忆增强。

公开(公告)号：US06080873A

公开(公告)日：2000-06-27

申请号：US148247

申请日：1998-09-04

申请人： Pamela Albaugh ,  Gang Liu ,  Kenneth Shaw ,  Alan Hutchison

发明人： Pamela Albaugh ,  Gang Liu ,  Kenneth Shaw ,  Alan Hutchison

IPC分类号： A61K31/00 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/538 ,  A61P25/00 ,  A61P25/04 ,  A61P43/00 ,  C07D209/42 ,  C07D209/52 ,  C07D401/12 ,  C07D403/10 ,  C07D405/12 ,  C07D413/12 ,  C07D209/14 ,  C07D209/34 ,  C07D209/40

CPC分类号： C07D401/12 ,  C07D209/42 ,  C07D209/52 ,  C07D405/12 ,  C07D413/12

摘要： The present invention encompasses structures of the formula I: ##STR1## or the pharmaceutically acceptable non-toxic salts thereof wherein: G represents ##STR2## where Q is aryl substituents optionally mono or disubstituted with hydroxy or halogen;T is halogen, hydrogen, hydroxyl, amino or alkoxy having 1-6 carbon atoms;W is oxygen, nitrogen, sulfur, or optionally substituted methylene;X is hydrogen, hydroxyl, or alkyl;Z is an organic or inorganic substituent optionally forming a ring with subtituents on Q; ##STR3## independently represent optionally substituted carbon chains; wherein k, m, and n are independently 0, or an integer of from 1-3R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are the same or different and represent organic or inorganic substituents.These compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAa brain receptors. These compounds are useful in the diagnosis and treatment of anxiety, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory.

摘要翻译： 本发明包括式I的结构：或其药学上可接受的无毒盐，其中：G表示其中Q是任选被羟基或卤素单取代或二取代的芳基取代基; T是卤素，氢，羟基，氨基或具有1-6个碳原子的烷氧基; W是氧，氮，硫或任选取代的亚甲基; X是氢，羟基或烷基; Z是任选地在Q上形成取代基的环的有机或无机取代基; 独立地代表任选取代的碳链; 其中k，m和n独立地为0，或1-3的整数，R3，R4，R5和R6相同或不同，表示有机或无机取代基。 这些化合物是GABAa脑受体的高选择性激动剂，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。 这些化合物可用于诊断和治疗焦虑，睡眠和癫痫发作，用苯二氮卓类药物过量并用于记忆。

公开(公告)号：US5750702A

公开(公告)日：1998-05-12

申请号：US683066

申请日：1996-07-16

申请人： Pamela Albaugh ,  Alan Hutchison

发明人： Pamela Albaugh ,  Alan Hutchison

IPC分类号： A61K31/404 ,  C07C233/58 ,  C07D209/08 ,  C07D209/42 ,  C07D209/52 ,  C07D307/84 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/04 ,  C07D417/12 ,  C07D471/04 ,  C07D401/04

CPC分类号： C07D209/08 ,  A61K31/404 ,  C07D209/42 ,  C07D209/52 ,  C07D307/84 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/04 ,  C07D417/12 ,  C07D471/04

摘要： The present invention encompasses structures of the formula: ##STR1## or the pharmaceutically acceptable non-toxic salts thereof wherein: ##STR2## wherein: W represents substituted or unsubstituted phenyl; X is hydrogen, hydroxy or lower alkyl; T is hydrogen, halogen, hydroxy, nitro, amino or alkyl; R.sub.3 is hydrogen or an organic group; R.sub.4 is hydrogen or substituted or unsubstituted organic substituent; R.sub.5 and R.sub.6 represent organic, and inorganic substituents; and n is 1, 2, 3, or 4, which compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAa brain receptors. These compounds are useful in the diagnosis and treatment of anxiety, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory.

摘要翻译： 本发明包括下式的结构：其中：W代表取代或未取代的苯基;或其药学上可接受的无毒盐，其中：W代表取代或未取代的苯基; X是氢，羟基或低级烷基; T是氢，卤素，羟基，硝基，氨基或烷基; R3是氢或有机基团; R4是氢或取代或未取代的有机取代基; R5和R6代表有机和无机取代基; 和n为1,2,3或4，这些化合物是用于GABAa脑受体的高选择性激动剂，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。 这些化合物可用于诊断和治疗焦虑，睡眠和癫痫发作，用苯二氮卓类药物过量并用于记忆。

公开(公告)号：US06420365B1

公开(公告)日：2002-07-16

申请号：US09765159

申请日：2001-01-17

申请人： John M. Peterson ,  Alan Hutchison ,  Kenneth Shaw ,  Kevin Hodgetts ,  George D. Maynard ,  Richard Lew

发明人： John M. Peterson ,  Alan Hutchison ,  Kenneth Shaw ,  Kevin Hodgetts ,  George D. Maynard ,  Richard Lew

IPC分类号： A61K31435

CPC分类号： C07D471/04

摘要： Disclosed are compounds of the formula: or the pharmaceutically acceptable non-toxic salts thereof wherein A, B, C, D, Y, R1, R3, R4, R5, and R6 are variables defined herein, which compounds are modulators of Bradykinin B2 receptors. These compounds are useful in the diagnosis and treatment of renal diseases, heart failure, hypertension, Meniere's disease, vaginal inflammation and pain, peripheral circulatory disorders, climacteric disturbance, retinochoroidal circulatory disorders, myocardial ischemia, myocardial infarction, postmyocardial infarction syndrome, angina pectoris, restenosis after percutaneous transluminal coronary angioplasty, hepatitis, liver cirrhosis, pancreatitis, ileus, diabetes, diabetic complications, male infertility, glaucoma, pain, asthma, and rhinitis and for the increase of permeability of the blood-brain barrier or the blood-brain-tumor barrier.

摘要翻译： 公开了下式的化合物或其药学上可接受的无毒性盐，其中A，B，C，D，Y，R 1，R 3，R 4，R 5和R 6是本文定义的变量，该化合物是缓激肽B2受体的调节剂 。 这些化合物可用于诊断和治疗肾脏疾病，心力衰竭，高血压，梅尼埃病，阴道炎症和疼痛，外周循环障碍，更年期障碍，视网膜循环障碍，心肌缺血，心肌梗死，心肌梗死后综合征，心绞痛， 经皮腔内冠状动脉血管成形术，肝炎，肝硬化，胰腺炎，肠梗阻，糖尿病，糖尿病并发症，男性不育症，青光眼，疼痛，哮喘和鼻炎的再狭窄，以及增加血脑屏障或血脑屏障的渗透性， 肿瘤屏障。

公开(公告)号：US06358949B1

公开(公告)日：2002-03-19

申请号：US09540580

申请日：2000-03-31

申请人： Robert W. DeSimone ,  Alan Hutchison ,  Kenneth Shaw ,  George D. Maynard ,  John M. Peterson ,  Richard Lew ,  Harry L. Brielmann

发明人： Robert W. DeSimone ,  Alan Hutchison ,  Kenneth Shaw ,  George D. Maynard ,  John M. Peterson ,  Richard Lew ,  Harry L. Brielmann

IPC分类号： A61K315377

CPC分类号： C07D471/04

摘要： Disclosed are compounds of the formula: or the pharmaceutically acceptable non-toxic salts thereof wherein: A, B, C and D are N or CH; X is a bond or (un)substituted CH2; R1 is lower alkenyl or (un)substituted lower alkyl; R3 is lower alkyl; and R2, R4, R5, and R6 are variables defined herein; which compounds are useful in the diagnosis and treatment of renal diseases, heart failure, hypertension, Meniere's disease, vaginal inflammation and pain, peripheral circulatory disorders, climacteric disturbance, retinochoroidal circulatroy disorders, myocardial ischemia, myocardial infarction, postmyocardial infarction syndrome, angina pectoris, restenosis after percutaneous transluminal coronary angioplasty, hepatitis, liver cirrhosis, pancreatitis, ileus, diabetes, diabetic complications, male infertility or glaucoma, or for the increase of permeability of blood-brain barrier, pain, asthma, and rhinitis.

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，B，C和D是N或CH; X是一个或（un）取代的CH 2; R 1是低级烯基或（取代） 低级烷基; R3是低级烷基; 和R2，R4，R5和R6是本文定义的变量;这些化合物可用于诊断和治疗肾脏疾病，心力衰竭，高血压，梅尼埃病，阴道炎症和疼痛，外周循环障碍，更年期障碍，视网膜循环障碍， 心肌缺血，心肌梗死，心肌梗死后综合征，心绞痛，经皮腔内冠状动脉成形术后再狭窄，肝炎，肝硬化，胰腺炎，肠梗阻，糖尿病，糖尿病并发症，男性不育症或青光眼，或增加血脑屏障通透性 ，疼痛，哮喘和鼻炎。

公开(公告)号：US06509366B2

公开(公告)日：2003-01-21

申请号：US09764805

申请日：2001-01-17

申请人： Stanislaw Rachwal ,  Alan Hutchison ,  Kenneth Shaw ,  George D. Maynard ,  Xiao-shu He ,  Robert DeSimone ,  Kevin Hodgetts

发明人： Stanislaw Rachwal ,  Alan Hutchison ,  Kenneth Shaw ,  George D. Maynard ,  Xiao-shu He ,  Robert DeSimone ,  Kevin Hodgetts

IPC分类号： A61K314174

CPC分类号： C07D233/64 ,  C07D233/68 ,  C07D401/06

摘要： Disclosed are compounds of the formula: or the pharmaceutically acceptable non-toxic salts thereof wherein Y, R1, R2, R3, R4, R5, R6, R7 R7′ are variables defined herein, which compounds are modulators of Bradykinin B2 receptors. These compounds are therefore useful in the diagnosis and treatment of renal diseases, heart failure, hypertension, Meniere's disease, vaginal inflammation and pain, peripheral circulatory disorders, climacteric disturbance, retinochoroidal circulatory disorders, myocardial ischemia, myocardial infarction, postmyocardial infarction syndrome, angina pectoris, restenosis after percutaneous transluminal coronary angioplasty, hepatitis, liver cirrhosis, pancreatitis, ileus, diabetes, diabetic complications, male infertility, glaucoma, pain, asthma, and rhinitis, and for the increase of permeability of the blood-brain barrier or the blood-brain-tumor barrier.

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Y，R 1，R 2，R 3，R 4，R 5，R 6，R 7 R 7'是本文定义的变量，该化合物是缓激肽B2受体的调节剂。 因此，这些化合物可用于诊断和治疗肾脏疾病，心力衰竭，高血压，梅尼埃病，阴道炎症和疼痛，外周循环障碍，更年期障碍，视网膜循环障碍，心肌缺血，心肌梗死，心肌梗死后综合征，心绞痛 经皮腔内冠状动脉血管成形术，肝炎，肝硬化，胰腺炎，肠梗阻，糖尿病，糖尿病并发症，男性不育症，青光眼，疼痛，哮喘和鼻炎的再狭窄，以及增加血脑屏障或血液 - 脑肿瘤屏障。

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：US07041664B2

公开(公告)日：2006-05-09

申请号：US10868136

申请日：2004-06-14

申请人： Jun Yuan ,  George Maynard ,  Alan Hutchison

发明人： Jun Yuan ,  George Maynard ,  Alan Hutchison

IPC分类号： C07D401/04 ,  A61K31/47

CPC分类号： A61K31/47 ,  C07D215/50 ,  C07D401/04 ,  C07D453/06 ,  C07D491/10 ,  Y10S206/828

摘要： Disclosed are compounds of the formula: or pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof, wherein R1, R2, R3, X, Q1 and Q2 are defined herein, which compounds are ligands for neurokinin receptors, in particular NK-3 receptors, and are therefor useful in the treatment of a wide range of diseases or disorders including, but not limited to depression, anxiety, psychosis, obesity, pain, Parkinson's disease, Alzheimer's disease, neurodegenerative diseases, movement disorders, respiratory diseases, inflammatory diseases, neuropathy, immune disorders, migraine, biliary disfunction, and dermatitis.

摘要翻译： 公开了下式的化合物或其药学上可接受的盐或药学上可接受的溶剂化物，其中R 1，R 2，R 3，X， 本文定义Q 1和Q 2 2，这些化合物是神经激肽受体特别是NK-3受体的配体，并且可用于治疗广泛范围的 疾病或病症，包括但不限于抑郁症，焦虑症，精神病，肥胖症，疼痛，帕金森病，阿尔茨海默病，神经变性疾病，运动​​障碍，呼吸系统疾病，炎性疾病，神经病，免疫疾病，偏头痛，胆汁功能异常和皮炎。

公开(公告)号：US07037922B1

公开(公告)日：2006-05-02

申请号：US09914957

申请日：2000-03-10

申请人： Jun Yuan ,  George Maynard ,  Alan Hutchison

发明人： Jun Yuan ,  George Maynard ,  Alan Hutchison

IPC分类号： C07D471/04 ,  A61K31/435

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.

摘要翻译： 公开了式（I）化合物或其药学上可接受的无毒盐或其药学上可接受的溶剂合物，其中：（II）代表（a），（b），（c）或（d）和W，X，Y， B，C，D，E是本文所述的变量。 这些化合物是NK3受体或其前药的高选择性激动剂或拮抗剂。 本发明中包含的新型速激肽NK-3受体拮抗剂在治疗NK-3受体活化是重要的哺乳动物的中枢神经系统（CNS）和外周的疾病和疾病的广泛阵列中具有潜在的用途。

公开(公告)号：US06495688B2

公开(公告)日：2002-12-17

申请号：US09887206

申请日：2001-06-21

申请人： Jun Yuan ,  Alan Hutchison

发明人： Jun Yuan ,  Alan Hutchison

IPC分类号： C07D48704

CPC分类号： C07D471/04 ,  C07D487/04

摘要： Disclosed are compounds of formula wherein Ar represents an aryl or heteroaryl group; and R1, R2, R3, R4 and R5 represent organic or inorganic substituents, which compounds are highly selective partial agonists or antagonists at human CRF1 receptors and, thus, 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： 公开的化合物，其中Ar表示芳基或杂芳基; 并且R 1，R 2，R 3，R 4和R 5表示有机或无机取代基，所述化合物是人CRF1受体的高选择性部分激动剂或拮抗剂，因此可用于诊断和治疗应激相关疾病例如血清后应激障碍 （PTSD）以及抑郁，头痛和焦虑。