公开(公告)号：US5276034A

公开(公告)日：1994-01-04

申请号：US688193

申请日：1991-04-19

申请人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting ,  Calum B. MacFarlane ,  Serge Beranger ,  Robert J. Dow

发明人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting ,  Calum B. MacFarlane ,  Serge Beranger ,  Robert J. Dow

IPC分类号： C07D233/54 ,  C07D403/06 ,  A61K31/495 ,  A61K31/55 ,  C07D243/08 ,  C07D403/00

CPC分类号： C07D233/64 ,  C07D403/06 ,  Y10S514/821

摘要： Substituted imidazolyl-alkyl-piperazine and diazepine derivatives and the pharmaceutically acceptable salts thereof are useful for treating mammals having any of a variety of disease states. These disease states include: 1) diseases treated by direct neuronal protection, including focal and global ischemia, spinal injuries, and head trauma, and neurological diseases including Alzheimer's and Huntington's chorea; 2) uraemic and hyponatraemic encephalopathy; 3) diseases treated by diuresis; 4) diseases treated by calcium channel antagonism, including cardiovascular diseases (i.e. hypertension, angina, stable and unstable angina, Prinzmetal angina, arrhythmia, thrombosis, embolism, and congestive heart failure including chronic or acute cardiac failure), diseases characterized by ischemia of lower legs due to peripheral vascular disease (e.g., intermittent claudication), diseases characterized by spasms of smooth muscle (i.e., spasms of the ureter, spasms of the bladder, uterine cramps, and irritable bowel syndrome), and prevention of vasoconstriction and/or ischemic tissue damage during a surgical procedure (i.e., bypass grafts, angiography, angioplasty, organ preservation during transplant, hypertensive crisis or post operative hypertension).

摘要翻译： 取代的咪唑基 - 烷基 - 哌嗪和二氮杂衍生物及其药学上可接受的盐可用于治疗具有各种疾病状态的哺乳动物。 这些疾病状态包括：1）通过直接神经元保护治疗的疾病，包括局灶性和全身缺血，脊髓损伤和头部创伤，以及包括阿尔茨海默氏症和亨廷顿氏舞蹈病在内的神经疾病; 2）尿毒症和低钠血症脑病; 3）通过利尿治疗的疾病; 4）通过钙通道拮抗治疗的疾病，包括心血管疾病（即高血压，心绞痛，稳定型和不稳定性心绞痛，Prinzmetal心绞痛，心律失常，血栓形成，栓塞和充血性心力衰竭，包括慢性或急性心力衰竭），特征在于缺血性低 由于外周血管疾病（例如间歇性跛行）引起的腿部，以平滑肌痉挛为特征的疾病（即输尿管痉挛，膀胱痉挛，子宫痉挛和肠易激综合征），以及预防血管收缩和/或缺血 手术过程中的组织损伤（即旁路移植物，血管造影，血管成形术，移植期间器官保护，高血压危象或手术后高血压）。

公开(公告)号：US5043447A

公开(公告)日：1991-08-27

申请号：US260969

申请日：1988-10-21

申请人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting ,  Calum B. Macfarlane ,  Serge Beranger ,  Robert J. Dow

发明人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting ,  Calum B. Macfarlane ,  Serge Beranger ,  Robert J. Dow

IPC分类号： C07D233/54 ,  C07D403/06

CPC分类号： C07D233/64 ,  C07D403/06 ,  Y10S514/821

摘要： Substituted imidazolyl-alkyl-piperazine and diazepine derivatives of Formula A: ##STR1## wherein: R.sup.1 is aryl, lower alkyl, cycloalkyl or hydrogen;R.sup.2 is aryl, lower alkyl or hydrogen;R.sup.3 is lower alkyl, hydroxy, or hydrogen;R.sup.4 is aryl or hydrogen;R.sup.5 is aryl or hydrogen;m is two or three;n is zero, one or two,provided that when R.sup.3 is hydroxy, n is one or two; andq is zero, one, two, or three;and the pharmaceutically acceptable salts thereof, are useful for treating mammals having any of a variety of disease states including:diseases treated by direct neuronal protection, such as ischemia including focal and global ischemia, spinal injuries, head trauma, and neurological diseases such as Alzheimer's and Huntington's chorea;diseases treated by inhibition of sodium ion, such as uremic and hyponatremic encephalopathy; anddiseases treated with calcium channel antagonists, including:diseases treated by inhibiting cerebrovascular vasospasm and by cerebrovascular vasodilation, such as migraine, stroke, vasospasm due to subarachnoid hemorrhage, epilepsy or epileptic psychotic symptoms, and cerebrovascular ischemia induced by cocaine abuse; andcardiovascular diseases, such as hypertension, angina, stable and unstable angina, Prinzmetal angina, arrhythmia, thrombosis, embolism, and congestive heart failure such as chronic or acute cardiac failure; andischemia of lower legs due to peripheral vascular disease, e.g., intermittent claudication;spasms of smooth muscle: such as the ureter, the bladder, uterine cramps, diuresis, and irritable bowel syndrome; anduses during surgery: such as bypass grafts, angiography, angioplasty, organ preservation during transplant, hypertensive crisis, or post operative hypertension.

摘要翻译： 取代的咪唑基 - 烷基 - 哌嗪和式A的二氮杂衍生物：其中：R 1是芳基，低级烷基，环烷基或氢; R2是芳基，低级烷基或氢; R3是低级烷基，羟基或氢; R4是芳基或氢; R5是芳基或氢; m是两三个; n为零，一个或两个，条件是当R3为羟基时，n为1或2; q为零，一，二或三; 其可用于治疗具有各种疾病状态的哺乳动物，包括：通过直接神经元保护治疗的疾病，例如局部缺血和局部缺血，脊髓损伤，头部创伤和神经疾病如阿尔茨海默病 和亨廷顿舞蹈病; 通过抑制钠离子治疗的疾病，如尿毒症和低钠血症脑病; 用钙通道拮抗剂治疗的疾病包括：通过抑制脑血管血管痉挛和脑血管血管舒张治疗的疾病，如偏头痛，中风，蛛网膜下腔出血引起的血管痉挛，癫痫或癫痫精神病症状，以及可卡因滥用引起的脑血管缺血; 心血管疾病，如高血压，心绞痛，稳定型和不稳定型心绞痛，心律失常，心律失常，血栓形成，栓塞，充血性心力衰竭如慢性或急性心力衰竭; 和由于外周血管疾病例如间歇性跛行引起的小腿缺血; 平滑肌痉挛，如输尿管，膀胱，子宫痉挛，利尿，肠易激综合征; 并且在手术期间使用：例如旁路移植物，血管造影术，血管成形术，移植期间的器官保存，高血压危象或术后高血压。

公开(公告)号：US5514800A

公开(公告)日：1996-05-07

申请号：US124518

申请日：1993-09-20

申请人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting ,  Calum B. MacFarlane ,  Serge Beranger

发明人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting ,  Calum B. MacFarlane ,  Serge Beranger

IPC分类号： C07D233/54 ,  C07D403/06 ,  C07D243/08

CPC分类号： C07D233/64 ,  C07D403/06 ,  Y10S514/821

摘要： Substituted imidazolyl-alkyl-piperazine and diazepine derivatives of Formula A: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, m, n and q are defined as in the specification, and the pharmaceutically acceptable salts thereof. The compounds have calcium entry blocking activity with selectivity for cerebral blood vessels, and have protective activity against some of the deleterious effects resultant upon cerebral ischemia.

摘要翻译： 式A的取代的咪唑基 - 烷基 - 哌嗪和二氮杂衍生物：其中R 1，R 2，R 3，R 4，R 5，m，n和q如说明书中所定义，及其药学上可接受的盐。 该化合物具有对脑血管的选择性的钙进入阻断活性，并且具有抵抗由脑缺血引起的一些有害作用的保护作用。

公开(公告)号：US4829065A

公开(公告)日：1989-05-09

申请号：US42181

申请日：1987-04-24

申请人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting

发明人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting

IPC分类号： A61K31/495 ,  A61K31/55 ,  A61P7/06 ,  A61P7/10 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P25/00 ,  A61P25/08 ,  A61P25/28 ,  C07D233/54 ,  C07D233/64 ,  C07D403/06

CPC分类号： C07D233/64 ,  C07D403/06

摘要： Substituted imidazolyl-alkyl-piperazine and diazepine derivatives of Formula A: ##STR1## wherein: R.sup.1 is aryl, lower alkyl, cycloalkyl or hydrogen;R.sup.2 is aryl, lower alkyl or hydrogen;R.sup.3 is lower alkyl, hydroxy, or hydrogen;R.sup.4 is aryl or hydrogen;R.sup.5 is aryl or hydrogen;m is two or three;n is zero, one or two,provided that when R.sup.3 is hydroxy, n is one or two; andq is zero, one, two, or three;and the pharmaceutically acceptable salts thereof, are calcium channel antagonists useful for treating mammals having a variety of disease states, such as stroke, epilepsy, hypertension, angina, migraine, arrhythmia, thrombosis, embolism and also for treatment of spinal injuries.

公开(公告)号：US5010075A

公开(公告)日：1991-04-23

申请号：US505379

申请日：1990-04-06

申请人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting

发明人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting

IPC分类号： C07D233/54 ,  C07D403/06

CPC分类号： C07D233/64 ,  C07D403/06

摘要： Substituted imidazolyl-alkyl-piperazine and diazepine derivatives of Formula A: ##STR1## wherein: R.sup.1 is aryl, lower alkyl, cycloalkyl or hydrogen;R.sup.2 is aryl, lower alkyl or hydrogen;R.sup.3 is lower alkyl, hydroxy, or hydrogen;R.sup.4 is aryl or hydrogen;R.sup.5 is aryl or hydrogen;m is two or three;n is zero, one or two, provided that when R.sup.3 is hydroxy, n is one or two; andq is zero, one, two, or three;and the pharmaceutically acceptable salts thereof, are calcium channel antagonists useful for treating mammals having a variety of disease states, such as stroke, epilepsy, hypertension, angina, migraine, arrhythmia, thrombosis, embolism and also for treatment of spinal injuries.

摘要翻译： 取代的咪唑基 - 烷基 - 哌嗪和式A的二氮杂衍生物：其中：R 1是芳基，低级烷基，环烷基或氢; R2是芳基，低级烷基或氢; R3是低级烷基，羟基或氢; R4是芳基或氢; R5是芳基或氢; m是两三个; n为零，一个或两个，条件是当R3为羟基时，n为1或2; q为零，一，二或三; 和其药学上可接受的盐是可用于治疗具有各种疾病状态的哺乳动物（如中风，癫痫，高血压，心绞痛，偏头痛，心律失常，血栓形成，栓塞）以及脊髓损伤治疗的钙通道拮抗剂。

公开(公告)号：US4935417A

公开(公告)日：1990-06-19

申请号：US313656

申请日：1989-02-21

申请人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting

发明人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting

IPC分类号： C07D233/54 ,  C07D403/06

CPC分类号： C07D233/64 ,  C07D403/06

摘要： Substituted imidazolyl-alkyl-piperazine and diazepine derivatives of Formula A: ##STR1## wherein: R.sup.1 is aryl, lower alkyl, cycloalkyl or hydrogen;R.sup.2 is aryl, lower alkyl or hydrogen;R.sup.3 lower alkyl, hydroxy, or hydrogen;R.sup.4 aryl or hydrogen;R.sup.5 aryl or hydrogen;m is two or three;n is zero, one or two,provided that when R.sup.3 hydroxy, n is one or two; andq is zero, one, two, or three;and the pharmaceutically acceptable salts thereof, are calcium channel antagonists useful for treating mammals having a variety of disease states, such as stroke, epilipsy, hypertension, angina, migraine, arrhythmia, thrombosis, embolism and also for treatment of spinal injuries.

摘要翻译： 取代的咪唑基 - 烷基 - 哌嗪和式A的二氮杂衍生物：其中：R 1是芳基，低级烷基，环烷基或氢; R2是芳基，低级烷基或氢; R3低级烷基，羟基或氢; R4芳基或氢; R5芳基或氢; m是两三个; n为零，一或二，条件是当R3羟基，n为1或2时; q为零，一，二或三; 和其药学上可接受的盐是可用于治疗具有各种疾病状态的哺乳动物的钙通道拮抗剂，例如卒中，外延，高血压，心绞痛，偏头痛，心律失常，血栓形成，栓塞以及用于治疗脊柱损伤。

公开(公告)号：US5252736A

公开(公告)日：1993-10-12

申请号：US789230

申请日：1991-11-07

申请人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting

发明人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting

IPC分类号： C07D233/54 ,  C07D403/06 ,  A61K31/495 ,  C07D403/02

CPC分类号： C07D233/64 ,  C07D403/06

摘要： Substituted imidazolyl-alkyl-piperazine and diazepine derivatives of Formula A: ##STR1## wherein: R.sup.1 is aryl, lower alkyl, cycloalkyl or hydrogen;R.sup.2 is aryl, lower alkyl or hydrogen;R.sup.3 is lower alkyl, hydroxy, or hydrogen;R.sup.4 is aryl or hydrogen;R.sup.5 is aryl or hydrogen;m is two or three;n is zero, one or two, provided that when R.sup.3 is hydroxy, n is oneor two; andq is zero, one, two, or three;and the pharmaceutically acceptable salts thereof, are calcium channel antagonists useful for treating mammals having a variety of disease states, such as stroke, epilepsy, hypertension, angina, migraine, arrhythmia, thrombosis, embolism and also for treatment of spinal injuries.

摘要翻译： 取代的咪唑基 - 烷基 - 哌嗪和式A的二氮杂衍生物：其中：R 1是芳基，低级烷基，环烷基或氢; R2是芳基，低级烷基或氢; R3是低级烷基，羟基或氢; R4是芳基或氢; R5是芳基或氢; m是两三个; n为零，一个或两个，条件是当R3为羟基时，n为1或2; q为零，一，二或三; 和其药学上可接受的盐是可用于治疗具有各种疾病状态的哺乳动物（如中风，癫痫，高血压，心绞痛，偏头痛，心律失常，血栓形成，栓塞）以及脊髓损伤治疗的钙通道拮抗剂。

公开(公告)号：US5091428A

公开(公告)日：1992-02-25

申请号：US652141

申请日：1991-02-07

申请人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting

发明人： Jean C. Pascal ,  Chi-Ho Lee ,  Brian J. Alps ,  Henri Pinhas ,  Roger L. Whiting

IPC分类号： C07D233/54 ,  C07D403/06

CPC分类号： C07D233/64 ,  C07D403/06

摘要： Substituted imidazolyl-alkyl-piperazine and diazepine derivatives of Formula A: ##STR1## wherein: R.sup.1 is aryl, lower alkyl, cycloalkyl or hydrogen;R.sup.2 is aryl, lower alkyl or hydrogen;R.sup.3 is lower alkyl, hydroxy, or hydrogen;R.sup.4 is aryl or hydrogen;R.sup.5 is aryl or hydrogen;m is two or three;n is zero, one or two, provided that when R.sup.3 is hydroxy, n is one or two; andq is zero, one, two, or three;and the pharmaceutically acceptable salts thereof, are calcium channel antagonists useful for treating mammals having a variety of disease states, such as stroke, epilepsy, hypertension, angina, migraine, arrhythmia, thrombosis, embolism and also for treatment of spinal injuries.

摘要翻译： 取代的咪唑基 - 烷基 - 哌嗪和式A的二氮杂衍生物：其中：R 1是芳基，低级烷基，环烷基或氢; R2是芳基，低级烷基或氢; R3是低级烷基，羟基或氢; R4是芳基或氢; R5是芳基或氢; m是两三个; n为零，一个或两个，条件是当R3为羟基时，n为1或2; q为零，一，二或三; 和其药学上可接受的盐是可用于治疗具有各种疾病状态的哺乳动物（如中风，癫痫，高血压，心绞痛，偏头痛，心律失常，血栓形成，栓塞）以及脊髓损伤治疗的钙通道拮抗剂。

公开(公告)号：US4259334A

公开(公告)日：1981-03-31

申请号：US27475

申请日：1979-04-05

申请人： Jean C. Pascal ,  Henri Pinhas

发明人： Jean C. Pascal ,  Henri Pinhas

IPC分类号： C07D295/12 ,  A61K31/495 ,  A61P9/06 ,  C07C43/225 ,  C07D295/02 ,  C07D295/03 ,  C07D295/092 ,  C07D295/195 ,  C07D295/08

CPC分类号： C07D295/03 ,  C07C43/225 ,  C07D295/088 ,  C07D295/195

摘要： The invention relates to compounds having the formula: ##STR1## in which: the substituents R.sub.1, R.sub.2 and R.sub.3 represent independently from each other a hydrogen atom, a halogen atom, a trifluoromethyl radical, a saturated or unsaturated straight- or branched-chain C.sub.1-6 alkyl radical, a C.sub.1-6 alkoxy radical the alkyl moiety of which may be saturated or unsaturated and straight- or branched-chained, a benzyloxy radical or a hydroxy radical;the substituents R.sub.5, R.sub.6 and R.sub.7 represent independently from each other a hydrogen atom, a halogen atom, a trifluoromethyl radical, a straight- or branched-chain saturated or unsaturated C.sub.1-6 alkyl radical, a C.sub.1-6 alkoxy radical the alkyl moiety of which may be saturated or unsaturated and straight- or branched-chained, or a hydroxy radical;the substituent R.sub.4 represents a hydrogen atom, a C.sub.1-6 alkyl radical or a hydroxy radical,m and n represent independently a number equal to 0, 1 or 2,X represents an oxygen atom, a sulfur atom or a single bond, and their pharmaceutically acceptable acid addition salts.These compounds are therapeutically useful for the control of the cardiovascular system.

摘要翻译： 本发明涉及具有下式的化合物：其中：取代基R 1，R 2和R 3彼此独立地表示氢原子，卤素原子，三氟甲基，饱和或不饱和的直链或支链 链C 1-6烷基，C 1-6烷氧基，其烷基部分可以是饱和或不饱和的，直链或支链的，苄氧基或羟基; 取代基R5，R6和R7彼此独立地表示氢原子，卤原子，三氟甲基，直链或支链饱和或不饱和的C1-6烷基，C1-6烷氧基，烷基部分 其可以是饱和或不饱和的直链或支链或羟基; 取代基R 4表示氢原子，C 1-6烷基或羟基，m和n独立地表示等于0,1或2的数，X表示氧原子，硫原子或单键， 药学上可接受的酸加成盐。 这些化合物在治疗上可用于控制心血管系统。