公开(公告)号：US6150367A

公开(公告)日：2000-11-21

申请号：US954516

申请日：1997-10-20

申请人： Neelima Sinha ,  Sanjay Jain ,  Anil Kumar Saxena ,  Nitya Anand ,  Ram Mohan Saxena ,  Mangal Prasad Dubey ,  Madhur Ray ,  Gyanendra K. Patnaik, deceased

发明人： Neelima Sinha ,  Sanjay Jain ,  Anil Kumar Saxena ,  Nitya Anand ,  Ram Mohan Saxena ,  Mangal Prasad Dubey ,  Madhur Ray ,  Gyanendra K. Patnaik, deceased

IPC分类号： C07D207/26 ,  C07D207/27 ,  C07D211/76 ,  A61K31/496 ,  C07D401/06 ,  C07D401/14 ,  C07D403/06

CPC分类号： C07D207/27 ,  C07D211/76

摘要： A chemical compound and composition of Formula 1: ##STR1## wherein Ar represents a phenyl ring substituted by the groups like halo, alkoxy, alkyl or heteroaryl, n=1 or n=2; said compounds and compositions as being useful therapeutic agents for hypertension, ischemic, cardiovascular and other adrenergic receptor related disorders.

摘要翻译： 式1的化合物和组合物：其中Ar表示被诸如卤素，烷氧基，烷基或杂芳基的基团取代的苯环，n = 1或n = 2; 所述化合物和组合物作为高血压，缺血性，心血管和其它肾上腺素能受体相关疾病的有用治疗剂。

公开(公告)号：US6084097A

公开(公告)日：2000-07-04

申请号：US960335

申请日：1997-10-29

申请人： Neelima Sinha ,  Sanjay Jain ,  Anil Kumar Saxena ,  Nitya Anand ,  Ram Mohan Saxena ,  Mangal Prasad Dubey ,  Madhur Ray ,  Gyanendra Kumar Patnaik, deceased

发明人： Neelima Sinha ,  Sanjay Jain ,  Anil Kumar Saxena ,  Nitya Anand ,  Ram Mohan Saxena ,  Mangal Prasad Dubey ,  Madhur Ray ,  Gyanendra Kumar Patnaik, deceased

IPC分类号： C07D207/26 ,  C07D207/27 ,  C07D211/76 ,  C07D401/06 ,  C07D401/14 ,  C07D403/06

CPC分类号： C07D211/76 ,  C07D207/27

摘要： The invention relates to a process for the synthesis of 1-[4-Arylpiperazin-1-yl]-3-[2-oxopyrrolidin/piperidin-1-yl]propanes used as potential therapeutic agents for hypertension, ischemia, cardiovascular and other adrenergic receptors related disorders, having general formula 1 ##STR1## wherein Ar represents a phenyl ring substituted by the groups like halo, alkoxy, alkyl or heteroaryl, n=1 or n=2; a process of preparing said compounds and a method of treating hypertension, ischemia, cardiovascular and other adrenergic receptors related disorders.

摘要翻译： 本发明涉及用作高血压，缺血，心血管和其他肾上腺素能潜在治疗剂的1- [4-芳基哌嗪-1-基] -3- [2-氧代吡咯烷/哌啶-1-基]丙烷的合成方法 受体相关疾病，具有通式1，其中Ar表示被诸如卤素，烷氧基，烷基或杂芳基的基团取代的苯环，n = 1或n = 2; 制备所述化合物的方法和治疗高血压，缺血，心血管和其它肾上腺素能受体相关疾病的方法。

公开(公告)号：US06812344B1

公开(公告)日：2004-11-02

申请号：US09578239

申请日：2000-05-24

申请人： Nitya Anand ,  Neelima Sinha ,  Sanjay Jain ,  Anita Mehta ,  Anil Kumar Saxena

发明人： Nitya Anand ,  Neelima Sinha ,  Sanjay Jain ,  Anita Mehta ,  Anil Kumar Saxena

IPC分类号： C07D40106

CPC分类号： C07D207/404 ,  A61K31/496 ,  C07D207/408 ,  C07D211/88 ,  C07D401/06

摘要： The present invention relates to certain novel piperazine derivatives having protracted uro-selective &agr;1-adrenoceptor antagonistic activity exceeding those of previously described compounds. The compounds of the present invention hold promise for treating benign prostratic hyperplasia (BPH). This invention also relates to methods for making the novel compounds, pharmaceutical compositions containing the compounds, and methods of treating benign prostatic hyperplasia using the compounds.

摘要翻译： 本发明涉及某些具有延长的尿选择性α1-肾上腺素能受体拮抗活性的新型哌嗪衍生物，超过前述化合物。 本发明化合物具有治疗良性前列腺增生（BPH）的希望。 本发明还涉及制备新化合物的方法，含有该化合物的药物组合物，以及使用该化合物治疗良性前列腺增生的方法。

公开(公告)号：US06410735B1

公开(公告)日：2002-06-25

申请号：US09578088

申请日：2000-05-24

申请人： Nitya Anand ,  Neelima Sinha ,  Sanjay Jain ,  Anita Mehta ,  Anil Kumar Saxena

发明人： Nitya Anand ,  Neelima Sinha ,  Sanjay Jain ,  Anita Mehta ,  Anil Kumar Saxena

IPC分类号： C07D40114

CPC分类号： C07D207/404 ,  A61K31/496 ,  C07D207/408 ,  C07D211/88 ,  C07D401/06

摘要： Novel piperzine derivatives substituted on one nitrogen by an aromatic system and on the other nitrogen by (2,5-dioxopyrrolidin)-1-yl) alkanes or (2,6-dioxopiperidin-1-yl) alkanes have been found to exhibit selective &agr;1A adrenergic activity. The compounds are useful for treatment of disease conditions, such as peripheral vascular disease, congestive heart failure, hypertension and especially benign prostatic hypertrophy.

摘要翻译： 已经发现，通过芳族系统在一个氮上取代的新颖的哌嗪衍生物，另一个氮被（2,5-二氧代吡咯烷-1-基）烷烃或（2,6-二氧代哌啶-1-基）烷烃取代，表现出选择性的α1A 肾上腺素能活动 该化合物可用于治疗疾病状况，例如外周血管疾病，充血性心力衰竭，高血压，特别是良性前列腺肥大。

公开(公告)号：US06420559B1

公开(公告)日：2002-07-16

申请号：US09577789

申请日：2000-05-24

申请人： Nitya Anand ,  Neelima Sinha ,  Sanjay Jain ,  Anita Mehta ,  Anil Kumar Saxena

发明人： Nitya Anand ,  Neelima Sinha ,  Sanjay Jain ,  Anita Mehta ,  Anil Kumar Saxena

IPC分类号： C07D40106

CPC分类号： C07D207/404 ,  A61K31/496 ,  C07D207/408 ,  C07D211/88 ,  C07D401/06

摘要： Novel piperzine derivatives substituted on one nitrogen by an aromatic system and on the other nitrogen by (2,5-dioxopyrrolidin)-1-yl) alkanes or (2,6-dioxopiperidin-1-yl) alkanes have been found to exhibit selective &agr;1A adrenergic activity. The compounds are useful for treatment of disease conditions, such as peripheral vascular disease, congestive heart failure, hypertension and especially benign prostatic hypertrophy.

摘要翻译： 已经发现，通过芳族系统在一个氮上取代的新颖的哌嗪衍生物，另一个氮被（2,5-二氧代吡咯烷-1-基）烷烃或（2,6-二氧代哌啶-1-基）烷烃取代，表现出选择性的α1A 肾上腺素能活动 该化合物可用于治疗疾病状况，例如外周血管疾病，充血性心力衰竭，高血压，特别是良性前列腺肥大。

公开(公告)号：US6090809A

公开(公告)日：2000-07-18

申请号：US203855

申请日：1998-12-02

申请人： Nitya Anand ,  Neelima Sinha ,  Sanjay Jain ,  Anita Mehta ,  Anil Kumar Saxena

发明人： Nitya Anand ,  Neelima Sinha ,  Sanjay Jain ,  Anita Mehta ,  Anil Kumar Saxena

IPC分类号： A61K31/496 ,  C07D207/40 ,  C07D207/404 ,  C07D207/408 ,  C07D211/88 ,  C07D401/06 ,  C07D403/06

CPC分类号： C07D207/404 ,  A61K31/496 ,  C07D207/408 ,  C07D211/88 ,  C07D401/06

摘要： Novel piperzine derivatives substituted on one nitrogen by an aromatic system and on the other nitrogen by (2,5-dioxopyrrolidin)-1-yl) alkanes or (2,6-dioxopiperidin-1-yl) alkanes have been found to exhibit selective .alpha..sub.1A adrenergic activity. The compounds are useful for treatment of disease conditions, such as peripheral vascular disease, congestive heart failure, hypertension and especially benign prostatic hypertrophy.

摘要翻译： 已经发现通过芳族体系在一个氮上取代的新颖的哌嗪衍生物，在另一个氮上被（2,5-二氧代吡咯烷-1-基）烷烃或（2,6-二氧代哌啶-1-基）烷烃取代，表现出选择性的α 1A肾上腺素能活动。 该化合物可用于治疗疾病状况，如外周血管疾病，充血性心力衰竭，高血压，特别是良性前列腺肥大。

公开(公告)号：US06420366B1

公开(公告)日：2002-07-16

申请号：US09577788

申请日：2000-05-24

申请人： Nitya Anand ,  Neelima Sinha ,  Sanjay Jain ,  Anita Mehta ,  Jang Bahadur Gupta

发明人： Nitya Anand ,  Neelima Sinha ,  Sanjay Jain ,  Anita Mehta ,  Jang Bahadur Gupta

IPC分类号： A61K31495

CPC分类号： C07D207/404 ,  A61K31/496 ,  C07D207/408 ,  C07D211/88 ,  C07D401/06

摘要： Novel piperzine derivatives substituted on one nitrogen by an aromatic system and on the other nitrogen by (2,5-dioxopyrrolidin)-1-yl) alkanes or (2,6-dioxopiperidin-1-yl) alkanes have been found to exhibit selective &agr;1A adrenergic activity. The compounds are useful for treatment of disease conditions, such as peripheral vascular disease, congestive heart failure, hypertension and especially benign prostatic hypertrophy.

摘要翻译： 已经发现，通过芳族系统在一个氮上取代的新颖的哌嗪衍生物，另一个氮被（2,5-二氧代吡咯烷-1-基）烷烃或（2,6-二氧代哌啶-1-基）烷烃取代，表现出选择性的α1A 肾上腺素能活动 该化合物可用于治疗疾病状况，例如外周血管疾病，充血性心力衰竭，高血压，特别是良性前列腺肥大。

公开(公告)号：US06914064B2

公开(公告)日：2005-07-05

申请号：US09998115

申请日：2001-11-30

申请人： Nitya Anand ,  Sanjay Jain ,  Neelima Sinha ,  Anita Chugh ,  Laxminarayan G. Hegde ,  Jang Bahadur Gupta

发明人： Nitya Anand ,  Sanjay Jain ,  Neelima Sinha ,  Anita Chugh ,  Laxminarayan G. Hegde ,  Jang Bahadur Gupta

IPC分类号： A61K31/497 ,  A61P13/08 ,  A61P43/00 ,  C07D209/48 ,  A61K31/496 ,  C07D403/06

CPC分类号： C07D209/48

摘要： The present invention relates to a novel 1,4-disubstituted piperazine derivatives of Formula I, and their pharmaceutically acceptable acid addition salts having excellent uro-selective α1-adrenoceptor antagonistic activity exceeding those of previously described compounds. The compounds of the present invention hold promise for treating the symptoms of benign prostatic hyperplasia (BPH). The invention also relates to methods for making the novel compounds, pharmaceutical compositions containing the compounds, and method of treating the symptoms of benign prostatic hyperplasia using the compounds.

摘要翻译： 本发明涉及式I的新型1,4-二取代哌嗪衍生物及其药学上可接受的酸加成盐，其具有超过前述化合物的优异的尿选择性α1 - 肾上腺素受体拮抗活性。 本发明的化合物有望治疗良性前列腺增生（BPH）的症状。 本发明还涉及制备新化合物的方法，含有该化合物的药物组合物，以及使用该化合物治疗良性前列腺增生症状的方法。

公开(公告)号：US6083950A

公开(公告)日：2000-07-04

申请号：US120265

申请日：1998-07-21

申请人： Nitya Anand ,  Neelima Sinha ,  Sanjay Jain ,  Anita Mehta ,  Jang Bahadurgupta

发明人： Nitya Anand ,  Neelima Sinha ,  Sanjay Jain ,  Anita Mehta ,  Jang Bahadurgupta

IPC分类号： A61K31/496 ,  C07D207/40 ,  C07D207/404 ,  C07D207/408 ,  C07D211/88 ,  C07D401/06 ,  A61K31/495

CPC分类号： C07D207/404 ,  A61K31/496 ,  C07D207/408 ,  C07D211/88 ,  C07D401/06

摘要： Novel piperzine derivatives substituted on one nitrogen by an aromatic system and on the other nitrogen by (2,5-dioxopyrrolidin)-1-yl) alkanes or (2,6-dioxopiperidin-1-yl) alkanes have been found to exhibit selective .alpha..sub.1A adrenergic activity. The compounds are useful for treatment of disease conditions, such as peripheral vascular disease, congestive heart failure, hypertension and especially benign prostatic hypertrophy.

摘要翻译： 已经发现通过芳族体系在一个氮上取代的新颖的哌嗪衍生物，在另一个氮上被（2,5-二氧代吡咯烷-1-基）烷烃或（2,6-二氧代哌啶-1-基）烷烃取代，表现出选择性的α 1A肾上腺素能活动。 该化合物可用于治疗疾病状况，例如外周血管疾病，充血性心力衰竭，高血压，特别是良性前列腺肥大。

公开(公告)号：US20090118509A1

公开(公告)日：2009-05-07

申请号：US11911272

申请日：2006-04-05

申请人： Sudershan Kumar Arora ,  Neelima Sinha ,  Sanjay Jain ,  Ram Shankar Upadhayaya ,  Om Dutt Tyagi ,  Vasanth Nalam ,  Yogendra Kumar Chauhan

发明人： Sudershan Kumar Arora ,  Neelima Sinha ,  Sanjay Jain ,  Ram Shankar Upadhayaya ,  Om Dutt Tyagi ,  Vasanth Nalam ,  Yogendra Kumar Chauhan

IPC分类号： C07D401/14

CPC分类号： C07D207/50 ,  C07D207/335 ,  C07D401/04 ,  C07D401/12

摘要： A process for the preparation of compounds of Formula I and their pharmaceutically acceptable acid addition salt wherein, R1 is phenyl or substituted phenyl R2 is selected from a group consisting of phenyl which is unsubstituted or substituted with 1 or 2 substituents, each independently selected from Cl, F, or pyridine, or naphthalene, or NHCOR4 wherein R4 is aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heterocyclyl. R3 is selected from a group of formula wherein R5 is phenyl which is unsubstituted or substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, amino, haloalkyl, haloalkoxy etc.; unsubstituted or substituted benzyl; unsubstituted or substituted heteroaryl; unsubstituted or substituted heteroaroyl; unsubstituted or substituted diphenylmethyl, n=0-2 and X═—NCH3, CH2, S, SO, or SO2 Such that when R2 is phenyl, which is unsubstituted or substituted with 1 or 2 substituents, each independently selected from Cl, F; R5 is not C1-C4 alkyl, or X is not —NCH3, CH2, S, SO, or SO2, when n=1, or X is not —CH2 when n=0; comprising the steps of (a) reacting compound of Formula II with a chlorinating agent in the presence or absence of catalytic amount of N,N-dimethylformamide to yield the compound of Formula III, (b) reacting the compound of Formula III with a compound of Formula R1H (R1 is as defined above), in presence of a Lewis acid to obtain the compound of Formula IV, (c) reacting the compound of Formula IV with a compound of Formula R2NH2 (R2 is as defined above) in presence of catalytic amounts of an aryl or alkyl sulphonic acid in an organic solvent to obtain the compound of Formula V, (d) reacting the compound of Formula V with various secondary amines of the Formula R3H (R3 is as defined above) in the presence of formaldehyde and acetic acid in acetonitrile followed by crystallization yield the compound of Formula I, (e) purifying the compound of Formula I by crystallization, (f) converting the purified compound of Formula I to a pharmaceutically acceptable acid addition salt.