公开(公告)号：US6103735A

公开(公告)日：2000-08-15

申请号：US412621

申请日：1999-10-06

申请人： Robert G. Aslanian ,  John J. Piwinski

发明人： Robert G. Aslanian ,  John J. Piwinski

IPC分类号： A61K45/06 ,  A61K31/44 ,  A61K31/415 ,  A61K31/445

CPC分类号： A61K45/06

摘要： The present invention is directed towards a pharmaceutical composition useful for the treatment of allergic rhinitis, asthma and related disorders. In one embodiment, the composition comprises, in combination, a therapeutically effective amount of at least one neurokinin antagonist, a therapeutically effective amount of at least one H.sub.3 antagonist and a therapeutically effective amount of at least one H.sub.1 antagonist.

摘要翻译： 本发明涉及可用于治疗过敏性鼻炎，哮喘和相关疾病的药物组合物。 在一个实施方案中，组合物组合包含治疗有效量的至少一种神经激肽拮抗剂，治疗有效量的至少一种H3拮抗剂和治疗有效量的至少一种H1拮抗剂。

公开(公告)号：US06034251A

公开(公告)日：2000-03-07

申请号：US185972

申请日：1998-11-05

申请人： Robert G. Aslanian ,  Kevin D. McCormick ,  John J. Piwinski

发明人： Robert G. Aslanian ,  Kevin D. McCormick ,  John J. Piwinski

IPC分类号： C07D233/54 ,  C07D233/60 ,  C07D233/61 ,  C07D233/90 ,  A61K31/415

CPC分类号： C07D233/64

摘要： Disclosed are novel phenyl-alkyl-imidazoles of the formula ##STR1## wherein R.sup.1, R.sup.7, m, n, p, q, X, Y, Z, R and R.sup.15 are as defined in the specification.Also disclosed are pharmaceutical compositions comprising the compounds of formula I.Further disclosed are methods of treating allergy, inflammation, hypotension, glaucoma, sleeping disorders, states of hyper and hypo motility of the gastrointestinal tract, hypo and hyperactivity of the central nervous system, Alzheimer's, schizophrenia, obesity and migraines by administering compounds of formula I.Also disclosed are methods for treatment of upper airway allergic responses comprising administering a compound, or salt or solvate thereof, of formula I in combination or admixture with a histamine H.sub.1 receptor antagonist.

摘要翻译： 公开了下式的新型苯基 ​​- 烷基 - 咪唑：其中R1，R7，m，n，p，q，X，Y，Z，R和R15如说明书中所定义。 还公开了包含式I化合物的药物组合物。进一步公开的是治疗过敏，炎症，低血压，青光眼，睡眠障碍，胃肠道超低运动状态，中枢神经系统低血压和多动症，阿尔茨海默病 ，精神分裂症，肥胖症和偏头痛。还公开了治疗上呼吸道过敏反应的方法，包括与组胺H1受体拮抗剂组合或混合施用式I化合物或其盐或溶剂合物。

公开(公告)号：US06528522B2

公开(公告)日：2003-03-04

申请号：US09954863

申请日：2001-09-18

申请人： Neng-Yang Shih ,  Robert G. Aslanian ,  John J. Piwinski ,  Andrew T. Lupo, Jr. ,  Adriano Afonso

发明人： Neng-Yang Shih ,  Robert G. Aslanian ,  John J. Piwinski ,  Andrew T. Lupo, Jr. ,  Adriano Afonso

IPC分类号： A61K31435

CPC分类号： C07D401/12 ,  C07D401/14

摘要： The present invention discloses novel substituted imidazole compounds which have H3 receptor antagonist activity or dual histamine-H1 and H3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy, congestion, inflammatory and CNS-related diseases and others.

公开(公告)号：US5840725A

公开(公告)日：1998-11-24

申请号：US901028

申请日：1997-07-25

申请人： Gregory A. Reichard ,  Robert G. Aslanian ,  Cheryl A. Alaimo ,  Michael P. Kirkup ,  Andrew Lupo, Jr. ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  John J. Piwinski ,  Bandarpalle B. Shankar ,  Neng-Yang Shih ,  James M. Spitler ,  Pauline C. Ting ,  Ashit Ganguly ,  Nicholas I. Carruthers

发明人： Gregory A. Reichard ,  Robert G. Aslanian ,  Cheryl A. Alaimo ,  Michael P. Kirkup ,  Andrew Lupo, Jr. ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  John J. Piwinski ,  Bandarpalle B. Shankar ,  Neng-Yang Shih ,  James M. Spitler ,  Pauline C. Ting ,  Ashit Ganguly ,  Nicholas I. Carruthers

IPC分类号： C07D295/12 ,  A61K31/397 ,  A61K31/40 ,  A61K31/415 ,  A61K31/4178 ,  A61K31/439 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4436 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4468 ,  A61K31/45 ,  A61K31/451 ,  A61K31/452 ,  A61K31/4523 ,  A61K31/4525 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/496 ,  A61K31/497 ,  A61K31/501 ,  A61K31/505 ,  A61K31/506 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/5377 ,  A61P1/00 ,  A61P11/00 ,  A61P25/00 ,  A61P29/00 ,  A61P43/00 ,  C07D205/04 ,  C07D207/08 ,  C07D207/12 ,  C07D207/14 ,  C07D211/52 ,  C07D211/58 ,  C07D211/76 ,  C07D295/13 ,  C07D295/185 ,  C07D333/22 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D405/12 ,  C07D409/06 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D451/04 ,  C07D403/06

CPC分类号： C07D295/185 ,  C07D211/52 ,  C07D211/58 ,  C07D211/76 ,  C07D295/13 ,  C07D333/22 ,  C07D401/04 ,  C07D401/06 ,  C07D409/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

摘要： Compound represented by the structural formula ##STR1## or a pharmaceutically acceptable salt thereof, wherein: a is 0, 1, 2 or3; b, d and e are independently 0, 1 or 2; R is H, C.sub.1-6 alkyl, --OH or C.sub.2 -C.sub.6 hydroxyalkyl; A is an optionally substituted oxime, hydrazone or olefin; X is a bond, --C(O)--, --O--, --NR.sup.6 --, --S(O)e--, --N(R.sup.6)C(O)--, --C(O)N(R.sup.6)-- --OC(O)NR.sup.6 --, --OC(.dbd.S)NR.sup.6 --, --N(R.sup.6)C(.dbd.S)O--, --C(.dbd.NOR.sup.1)--, --S(O).sub.2 N(R.sup.6)--, --N(R.sup.6)S(O).sub.2 --, --N(R.sup.6)C(O)O-- or --OC(O)--;T is H, phthalimidyl, aryl, heterocycloalkyl, heteroaryl, cycloalkyl or bridged cycloalkyl; Q is --SR.sup.6, --N(R.sup.6)(R.sup.7), --OR.sup.6, phenyl, naphthyl or heteroaryl; R.sup.6a, R.sup.7a, R.sup.8a, R.sup.9a, R.sup.6 and R.sup.7 are H, C.sub.1-6 alkyl, C.sub.2 -C.sub.6 hydroxyalkyl, C.sub.1 -C.sub.6 alkoxy-C.sub.1 -C.sub.6 alkyl, phenyl or benzyl; or R.sup.6 and R.sup.7, together with the nitrogen to which they are attached, form a ring; R.sup.9a is R.sup.6 or --OR.sup.6 ; Z is morpholinyl, optionally N-substituted piperazinyl, optionally substituted ##STR2## or substituted ##STR3## g is 0-3 and h is 1-4, provided the sum of h and g is 1-7; wherein aryl, heterocycloalkyl, heteroaryl, cycloalkyl and bridged cycloalkyl groups are optionally substituted; methods of treating asthma, cough, bronchospasm, imflammatory diseases, and gastrointestinal disorders with said compounds, and pharmaceutical compositions comprising said compounds are disclosed.

摘要翻译： 由结构式I表示的化合物或其药学上可接受的盐，其中：a是0,1,2或3; b，d和e独立地为0,1或2; R为H，C 1-6烷基，-OH或C 2 -C 6羟基烷基; A是任选取代的肟，腙或烯烃; X是键，-C（O） - ， - O - ， - NR 6 - ， - S（O）e - ， - N（R 6）C（O） - ， - OC（O）NR6-， - OC（= S）NR6-，-N（R6）C（= S）O-，-C（= NOR1） - ， - S（O） （R 6）S（O）2 - ， - N（R 6）C（O）O-或-OC（O） - ; T是H，苯偶酰亚氨基，芳基，杂环烷基，杂芳基，环烷基或桥连环烷基; Q是-SR 6，-N（R 6）（R 7），-OR 6，苯基，萘基或杂芳基; R6a，R7a，R8a，R9a，R6和R7是H，C1-6烷基，C2-C6羟基烷基，C1-C6烷氧基-C1-C6烷基，苯基或苄基; 或R 6和R 7与它们所连接的氮一起形成环; R9a为R6或-OR6; Z是吗啉基，任选取代的哌嗪基，任选取代的取代的或取代的，如果h和g之和为1-7，则g是0-3，h是1-4; 其中芳基，杂环烷基，杂芳基，环烷基和桥连环烷基任选被取代; 公开了用所述化合物治疗哮喘，咳嗽，支气管痉挛，炎性疾病和胃肠道疾病的方法，以及包含所述化合物的药物组合物。

公开(公告)号：US20080119487A1

公开(公告)日：2008-05-22

申请号：US11943315

申请日：2007-11-20

申请人： Robert G. Aslanian ,  Neng-Yang Shih ,  Pauline C. Ting ,  Michael Y. Berlin ,  Stuart B. Rosenblum ,  Kevin D. McCormick ,  Wing C. Tom ,  Christopher W. Boyce ,  Pietro Mangiaracina ,  Mwangi W. Mutahi ,  John J. Piwinski

发明人： Robert G. Aslanian ,  Neng-Yang Shih ,  Pauline C. Ting ,  Michael Y. Berlin ,  Stuart B. Rosenblum ,  Kevin D. McCormick ,  Wing C. Tom ,  Christopher W. Boyce ,  Pietro Mangiaracina ,  Mwangi W. Mutahi ,  John J. Piwinski

IPC分类号： A61K31/495 ,  A61K31/445 ,  A61K31/435 ,  A61P27/14 ,  A61P11/02

CPC分类号： C07D213/73 ,  A61K31/435 ,  A61K31/445 ,  A61K31/495 ,  C07D401/12 ,  C07D401/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D498/04

摘要： Disclosed are novel compounds of the formula Also disclosed are pharmaceutical compositions comprising the compounds of Formula I.Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula I.Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula I in combination with a H1 receptor antagonist.

摘要翻译： 公开的是式的新化合物还公开了包含式I化合物的药物组合物。还公开了治疗各种疾病或病症的方法，例如过敏，过敏诱发的气道反应和充血（例如，鼻 拥塞）。还公开了使用组合式I化合物来治疗各种疾病或病症的方法，例如过敏，过敏诱发的气道反应和充血（例如，鼻塞） 具有H 1受体拮抗剂。

公开(公告)号：US07300941B2

公开(公告)日：2007-11-27

申请号：US10699189

申请日：2003-10-31

申请人： Robert G. Aslanian ,  Neng-Yang Shih ,  Pauline C. Ting ,  Michael Y. Berlin ,  Stuart B. Rosenblum ,  Kevin D. McCormick ,  Wing C. Tom ,  Christopher W. Boyce ,  Pietro Mangiaracina ,  Mwangi W. Mutahi ,  John J. Piwinski

发明人： Robert G. Aslanian ,  Neng-Yang Shih ,  Pauline C. Ting ,  Michael Y. Berlin ,  Stuart B. Rosenblum ,  Kevin D. McCormick ,  Wing C. Tom ,  Christopher W. Boyce ,  Pietro Mangiaracina ,  Mwangi W. Mutahi ,  John J. Piwinski

IPC分类号： A61K31/44

CPC分类号： C07D213/73 ,  A61K31/435 ,  A61K31/445 ,  A61K31/495 ,  C07D401/12 ,  C07D401/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D498/04

摘要： Disclosed are novel compounds of the formula Also disclosed are pharmaceutical compositions comprising the compounds of Formula I.Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula I.Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula I in combination with a H1 receptor antagonist.

摘要翻译： 公开的是式的新化合物还公开了包含式I化合物的药物组合物。还公开了治疗各种疾病或病症的方法，例如过敏，过敏诱发的气道反应和充血（例如，鼻 拥塞）。还公开了使用组合式I化合物来治疗各种疾病或病症的方法，例如过敏，过敏诱发的气道反应和充血（例如，鼻塞） 具有H 1受体拮抗剂。

公开(公告)号：US06720328B2

公开(公告)日：2004-04-13

申请号：US09978267

申请日：2001-10-15

申请人： Robert G. Aslanian ,  Neng-Yang Shih ,  Pauline C. Ting ,  Michael Y. Berlin ,  Stuart B. Rosenblum ,  Kevin D. McCormick ,  Wing C. Tom ,  Christopher W. Boyce ,  Pietro Mangiaracina ,  Mwangi W. Mutahi ,  John J. Piwinski

发明人： Robert G. Aslanian ,  Neng-Yang Shih ,  Pauline C. Ting ,  Michael Y. Berlin ,  Stuart B. Rosenblum ,  Kevin D. McCormick ,  Wing C. Tom ,  Christopher W. Boyce ,  Pietro Mangiaracina ,  Mwangi W. Mutahi ,  John J. Piwinski

IPC分类号： C07D40114

CPC分类号： C07D213/73 ,  A61K31/435 ,  A61K31/445 ,  A61K31/495 ,  C07D401/12 ,  C07D401/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D498/04

摘要： Disclosed are novel compounds of the formula In Formula I, M1 is carbon, M2, M3 and M4 are carbon or nitrogen and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of Formula I. Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula I. Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula I in combination with a H1 receptor antagonist.

摘要翻译： 公开了式I的新化合物，式I中M 1是碳，M 2，M 3和M 4是碳或氮，其余的变量如说明书中所定义。 还公开了包含式I化合物的药物组合物。还公开了使用式（I）的化合物治疗各种疾病或病症例如过敏，过敏诱发的气道反应和充血（例如，鼻塞）的方法 还公开了使用式I化合物与H1受体拮抗剂组合来治疗各种疾病或病症的方法，例如过敏，过敏诱导的气道反应和充血（例如，鼻塞）。

公开(公告)号：US06211182B1

公开(公告)日：2001-04-03

申请号：US09264615

申请日：1999-03-08

申请人： Wayne Vaccaro ,  John J. Piwinski ,  Wing C. Tom ,  Daniel M. Solomon ,  Robert G. Aslanian

发明人： Wayne Vaccaro ,  John J. Piwinski ,  Wing C. Tom ,  Daniel M. Solomon ,  Robert G. Aslanian

IPC分类号： A61K31496

CPC分类号： C07D233/64 ,  C07D401/12 ,  C07D401/14 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14

摘要： This invention discloses novel imidazoles substituted with a six or seven membered heterocyclic ring which contains two nitrogen atoms as part of the heterocyclic ring structure. These compounds have excellent histamine-H3 receptor antagonist activity. Also disclosed are methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy (for example asthma), inflammation, hypertension, raised intraocular pressure (such as glaucoma)—i.e., a method of lowering intraocular pressure, sleeping disorders, states of hyper and hypomotility and acidic secretion of the gastrointestinal tract, hypo and hyperactivity of the central nervous system (for example, agitation and depression) and other CNS disorders (such as Alzheimer's Disease, schizophrenia, and migraine). An illustrative inventive imidazole is shown below:

摘要翻译： 本发明公开了用含有两个氮原子作为杂环结构的一部分的六元或七元杂环取代的新型咪唑。 这些化合物具有优异的组胺H3受体拮抗剂活性。 还公开了制备这些化合物的方法。 在另一个实施方案中，本发明公开了包含这种咪唑的药物组合物以及使用它们治疗过敏（例如哮喘），炎症，高血压，升高的眼内压（如青光眼）的方法，降低眼内压的方法， 睡眠障碍，超低运动性和胃肠道酸性分泌状态，中枢神经系统（例如，激动和抑郁）和其他CNS疾病（如阿尔茨海默病，精神分裂症和偏头痛）的低反应和多动症。 本发明的咪唑如下所示：

公开(公告)号：US06762186B2

公开(公告)日：2004-07-13

申请号：US09955383

申请日：2001-09-18

申请人： Neng-Yang Shih ,  Robert G. Aslanian ,  Daniel M. Solomon ,  Stuart B. Rosenblum ,  Mwangi Wa Mutahi ,  Tom G. Wing ,  Kevin D. McCormick ,  John J. Piwinski ,  Ronald Wolin

发明人： Neng-Yang Shih ,  Robert G. Aslanian ,  Daniel M. Solomon ,  Stuart B. Rosenblum ,  Mwangi Wa Mutahi ,  Tom G. Wing ,  Kevin D. McCormick ,  John J. Piwinski ,  Ronald Wolin

IPC分类号： C07D21168

CPC分类号： C07D233/64 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/06

摘要： The present invention discloses novel substituted imidazole compounds which have H3 receptor antagonist or dual histamine-H1 and H3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy, nasal congestion, inflammatory and CNS-related diseases and others.

摘要翻译： 本发明公开了具有H3受体拮抗剂或双组胺H1和H3受体拮抗剂活性的新型取代咪唑化合物以及制备这些化合物的方法。 在另一个实施方案中，本发明公开了包含这种咪唑的药物组合物以及使用它们治疗过敏，鼻充血，炎性和CNS相关疾病等的方法。

公开(公告)号：US06518287B2

公开(公告)日：2003-02-11

申请号：US09955380

申请日：2001-09-18

申请人： Robert G. Aslanian ,  Stuart Rosenblum ,  Mwangi Wa Mutahi ,  Neng-Yang Shih ,  John J. Piwinski

发明人： Robert G. Aslanian ,  Stuart Rosenblum ,  Mwangi Wa Mutahi ,  Neng-Yang Shih ,  John J. Piwinski

IPC分类号： A61K314439

CPC分类号： C07D233/64 ,  C07D401/12 ,  C07D401/14

摘要： The present invention discloses novel substituted imidazole compounds which have either or dual histamine-H1 and H3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy, inflammatory and CNS-related diseases and others.