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1. 发明申请

WO1997041154A1 EOSINOPHIL EOTAXIN RECEPTOR 审中-公开
标题翻译： EOSINOPHIL爱可酮受体
公开(公告)号：WO1997041154A1
公开(公告)日：1997-11-06
申请号：PCT/US1997006568
申请日：1997-04-24
申请人： MERCK & CO., INC. , DAUGHERTY, Bruce, L. , DEMARTINO, Julie, A. , SPRINGER, Martin, S. , SICILIANO, Salvatore, J.
发明人： MERCK & CO., INC.
IPC分类号： C07K14/705
CPC分类号： C07K14/7158 , A61K38/00
摘要： The eosinophil eotaxin receptor has been isolated, cloned and sequenced. This receptor is a human beta -chemokine receptor and has been designated "CC CKR3". The eosinophil eotaxin receptor may be used to screen and identify compounds that bind to the eosinophil eotaxin receptor. Such compounds would be useful in the treatment and prevention of atopic conditions including allergic rhinitis, dermatis, conjunctivitis, and particularly bronchial asthma.
摘要翻译：已经分离，克隆和测序嗜酸性粒细胞嗜酸性粒细胞趋化因子受体。该受体是人β-胆碱酯受体，被称为“CC CKR3”。嗜酸性粒细胞嗜酸性粒细胞趋化因子受体可用于筛选和鉴定结合嗜酸性粒细胞嗜酸性粒细胞趋化嗜酸性粒细胞趋化因子受体的化合物。这些化合物可用于治疗和预防特应性疾病，包括过敏性鼻炎，皮肤病，结膜炎，特别是支气管哮喘。

2. 发明申请

WO2014113734A3 ISOMETHEPTENE ISOMER 审中-公开
标题翻译：异构体异构体
公开(公告)号：WO2014113734A3
公开(公告)日：2014-11-27
申请号：PCT/US2014012142
申请日：2014-01-17
申请人： TONIX PHARMACEUTICALS INC , LEDERMAN SETH , DAUGHERTY BRUCE , GERSHELL LELAND J , RIDEOUT DARRYL , KAWASAKI ANDREW
发明人： LEDERMAN SETH , DAUGHERTY BRUCE , GERSHELL LELAND J , RIDEOUT DARRYL , KAWASAKI ANDREW
IPC分类号： C07C211/21 , A61K31/131 , A61P29/00 , A61P37/00 , C07B55/00
CPC分类号： C07C211/21 , A61K31/047 , A61K31/131 , A61K31/167 , A61K31/192 , A61K31/4045 , A61K31/4152 , A61K31/522 , A61K31/616 , A61K45/06 , C07B53/00 , C07B2200/07 , C07C59/285 , A61K2300/00
摘要： The invention relates to a purified Isometheptene compound comprising the structure according to Formula (I), (Formula (I)) or a hydrochloride, or a pharmaceutically acceptable addition salt thereof. In particular, the disclosure relates to the synthesis, purification and characterization of an Isometheptene isomer mucate crystal 2, wherein the Isometheptene isomer 2 is stereochemically characterized as (R)-enantiomer, respectively. The Isometheptene (R)-enantiomer activity indicates a selective centrally acting selective ligand for Imidazoline subtype 1 (I1) receptor sites; and more specifically, the disclosure provides an antihypertensive composition for treatment of migraine and other neurovascular or neurogenic pain from abdominal distress. (R)-Isometheptene enantiomer or isomer 2 may be an anti-hypertensive agent with lower side effects than the racemate form. Therefore (R)-Isometheptene is believed to be effective against episodic tension-type headaches (ETTH). The (R)-Isometheptene enantiomer or isomer 2 is believed to effectively lower blood pressure, used alone or together with other headache ameliorating drugs. Methods of synthesis and treatment are described. Regarding (R)- Isometheptene crystals data of X-ray crystallography are presented.
摘要翻译：本发明涉及包含根据式（I），（式（I））的结构或盐酸盐或其药学上可接受的加成盐的纯化的异美汀化合物。特别地，本公开涉及异美金属异构体粘酸盐晶体2的合成，纯化和表征，其中异美金属异构体2分别立体化学表征为（R） - 对映体。 Isometheptene（R） - 对映体活性表示咪唑啉亚型1（I1）受体位点的选择性中心作用选择性配体; 更具体地说，本公开内容提供了用于治疗偏头痛和其他神经血管疼痛或神经源性疼痛免受腹部痛苦的抗高血压组合物。（R） - 异美辛对映异构体或异构体2可以是与外消旋体形式相比具有较低副作用的抗高血压剂。因此（R）-Isometheptene被认为对发作性紧张型头痛（ETTH）有效。据信（R）-Isometheptene对映异构体或异构体2可有效降低血压，单独使用或与其他头痛改善药物一起使用。描述了合成和处理的方法。关于（R） - 异美斯汀晶体的X射线晶体学数据的介绍。

3. 发明申请

WO2016105449A1 COMPOUNDS FOR USE AS PAIN THERAPEUTICS 审中-公开
标题翻译：用作止痛药的化合物
公开(公告)号：WO2016105449A1
公开(公告)日：2016-06-30
申请号：PCT/US2015/000154
申请日：2015-12-22
申请人： LEDERMAN, Seth , DAUGHERTY, Bruce
发明人： LEDERMAN, Seth , DAUGHERTY, Bruce
IPC分类号： C07D263/28 , C07D207/22 , C07D233/06 , C07D233/20 , C07D233/22 , C07D233/24 , C07D233/88 , C07D233/50 , C07D263/48 , C07D401/04 , C07D403/04 , C07D403/12 , C07D417/12 , C07D471/04 , C07C211/38 , C07D405/04 , C07C211/08 , C07C211/21 , C07C211/42 , C07C279/22 , C07C279/04 , C07H19/052 , A61K31/13 , A61K31/155 , A61K31/40 , A61K31/4164 , A61K31/4168 , A61K31/4178 , A61K31/421 , A61K31/43 , A61K31/4725 , A61K31/506 , A61K31/7028 , A61P29/00 , A61P29/02 , A61P43/00 , C07C279/12 , A61K31/417 , A61K31/4174
CPC分类号： C07H19/052 , A61K31/047 , A61K31/13 , A61K31/155 , A61K31/167 , A61K31/192 , A61K31/40 , A61K31/4164 , A61K31/4166 , A61K31/4168 , A61K31/417 , A61K31/4174 , A61K31/4178 , A61K31/421 , A61K31/427 , A61K31/437 , A61K31/4725 , A61K31/506 , A61K31/522 , A61K31/616 , A61K31/7008 , Y02A50/401 , A61K2300/00
摘要： This disclosure provides compounds and compositions for use as analgesics and for the treatment of one or more conditions selected from: pain; psychic pain; psychological pain; psychiatric pain; depression; allodynia; fibromyalgia; fibromyalgia-ness; central sensitization; centralization; regional pain syndrome; temporomandibular joint syndrome (TMJ); lower back pain; interstitial cystitis; Gulf War syndrome; visceral pain; phantom limb painj.kidney stones; gout; neuropathic pain; post-herpetic neuralgia; diabetic neuropathy; sickle cell pain; priapism; nociceptive pain; post-operative pain; orthopedic injury pain; bunionectomy; dental extraction; pain after severed spinal cord injury; osteoarthritis; rheumatoid arthritis; Lyme disease; Parkinson's disease; opioid-induced constipation; an opioid withdrawal symptom; pain associated with post-traumatic stress disorder (PTSD); and combinations of any of the foregoing conditions. This disclosure also provides compounds that are ligands, and in some embodiments, modulators (e.g., agonists), for the imidazoline receptor type 1.
摘要翻译：本公开提供用作止痛剂和用于治疗选自以下的一种或多种病症的化合物和组合物：疼痛; 精神痛苦心理上的痛苦; 精神病痛萧条; 异常性疼痛; 纤维肌痛; 纤维肌痛的烦躁; 中心致敏; 集权; 区域性疼痛综合征; 颞下颌关节综合征（TMJ）; 腰背痛间质性膀胱炎海湾战争综合症; 内脏痛幻肢四肢痛痛风; 神经性疼痛疱疹后神经痛糖尿病性神经病变镰状细胞性疼痛阴茎异常勃起; 伤害性疼痛术后疼痛; 矫形外伤性疼痛; 拇囊炎切除; 牙科提取; 切断脊髓损伤后疼痛; 骨关节炎; 类风湿关节炎; 莱姆病; 帕金森病阿片样物质引起的便秘阿片样物质戒断症状与创伤后应激障碍（PTSD）相关的疼痛; 以及任何上述条件的组合。本公开还提供了作为咪唑啉受体1型的配体，在一些实施方案中为调节剂（例如激动剂）的化合物。

4. 发明申请

WO2014113734A2 ISOMETHEPTENE ISOMER 审中-公开
标题翻译：异构异构体
公开(公告)号：WO2014113734A2
公开(公告)日：2014-07-24
申请号：PCT/US2014/012142
申请日：2014-01-17
申请人： TONIX PHARMACEUTICALS INC. , LEDERMAN, Seth , DAUGHERTY, Bruce , GERSHELL, Leland J. , RIDEOUT, Darryl , KAWASAKI, Andrew
发明人： LEDERMAN, Seth , DAUGHERTY, Bruce , GERSHELL, Leland J. , RIDEOUT, Darryl , KAWASAKI, Andrew
CPC分类号： C07C211/21 , A61K31/047 , A61K31/131 , A61K31/167 , A61K31/192 , A61K31/4045 , A61K31/4152 , A61K31/522 , A61K31/616 , A61K45/06 , C07B53/00 , C07B2200/07 , C07C59/285 , A61K2300/00
摘要： The invention relates to a purified Isometheptene compound comprising the structure according to Formula (I), (Formula (I)) or a hydrochloride, or a pharmaceutically acceptable addition salt thereof. In particular, the disclosure relates to the synthesis, purification and characterization of an Isometheptene isomer mucate crystal 2, wherein the Isometheptene isomer 2 is stereochemically characterized as (R)-enantiomer, respectively. The Isometheptene (R)-enantiomer activity indicates a selective centrally acting selective ligand for Imidazoline subtype 1 (I1) receptor sites; and more specifically, the disclosure provides an antihypertensive composition for treatment of migraine and other neurovascular or neurogenic pain from abdominal distress. (R)-Isometheptene enantiomer or isomer 2 may be an anti-hypertensive agent with lower side effects than the racemate form. Therefore (R)-Isometheptene is believed to be effective against episodic tension-type headaches (ETTH). The (R)-Isometheptene enantiomer or isomer 2 is believed to effectively lower blood pressure, used alone or together with other headache ameliorating drugs. Methods of synthesis and treatment are described. Regarding (R)- Isometheptene crystals data of X-ray crystallography are presented.
摘要翻译：本发明涉及包含根据式（I），（式（I））或盐酸盐的结构或其药学上可接受的加成盐的纯化异构体化合物。特别地，本公开涉及异葎草酮异构体粘蛋白晶体2的合成，纯化和表征，其中异构异构体异构体2分别被立体化学表征为（R） - 对映异构体。对映异构体异构体活性表示咪唑啉亚型1（I1）受体位点的选择性中心作用选择性配体; 并且更具体地，本公开提供了用于治疗偏头痛和其他神经血管或神经源性疼痛的抗高血压组合物。（R） - 异亚丙基对映异构体或异构体2可以是具有低于外消旋形式的副作用的抗高血压剂。因此（R） - 美沙芬被认为对于发作型紧张型头痛（ETTH）有效。据信（R） - 异构体异构体2有效地降低血压，单独使用或与其他头痛改善药物一起使用。描述合成和处理方法。关于（R） - 异构体色素晶体的X射线晶体学数据。

5. 发明申请

WO2016105448A1 IMIDAZOLINE RECEPTOR TYPE 1 LIGANDS FOR USE AS THERAPEUTICS 审中-公开
标题翻译：咪唑啉受体类型1用作治疗药物的配体
公开(公告)号：WO2016105448A1
公开(公告)日：2016-06-30
申请号：PCT/US2015/000153
申请日：2015-12-22
申请人： RIDEOUT, Darryl , LEDERMAN, Seth , DAUGHERTY, Bruce , GERSHELL, Leland, J.
发明人： RIDEOUT, Darryl , LEDERMAN, Seth , DAUGHERTY, Bruce , GERSHELL, Leland, J.
IPC分类号： C07D207/22 , C07C211/01 , C07C211/35 , C07C211/39 , C07C217/06 , C07C257/10 , C07C271/16 , C07C279/02 , C07C279/26 , C07D205/04 , C07D207/04 , C07D209/44 , C07D209/52 , C07D217/04 , C07D233/04 , C07D233/44 , C07D233/54 , C07D235/02 , C07D239/06 , C07D239/70 , C07D243/04 , C07D263/28 , C07D295/185 , C07D319/20 , C07D401/06 , C07D401/14 , C07D403/02 , C07D403/14 , C07D407/12 , C07D409/02 , C07D409/14 , C07D413/14 , C07D417/06 , C07D471/02 , C07K14/00 , C07K7/04 , A61K31/395 , A61K31/13 , A61K31/131 , A61K31/133 , A61K31/155 , A61K31/325 , A61K38/04 , A61K38/16
CPC分类号： A61K31/13 , A61K31/131 , A61K31/133 , A61K31/155 , A61K31/325 , A61K31/395 , A61K38/00 , C07C211/01 , C07C211/08 , C07C211/15 , C07C211/17 , C07C211/21 , C07C211/24 , C07C211/25 , C07C211/27 , C07C211/35 , C07C211/38 , C07C211/39 , C07C211/40 , C07C211/41 , C07C211/42 , C07C217/06 , C07C217/08 , C07C217/52 , C07C233/62 , C07C257/10 , C07C257/14 , C07C257/16 , C07C257/18 , C07C271/16 , C07C279/02 , C07C279/04 , C07C279/06 , C07C279/08 , C07C279/12 , C07C279/14 , C07C279/22 , C07C279/26 , C07C323/44 , C07C2601/02 , C07C2601/04 , C07C2601/08 , C07C2601/14 , C07C2602/08 , C07C2602/24 , C07D205/04 , C07D207/327 , C07D207/33 , C07D209/02 , C07D209/44 , C07D233/22 , C07D233/24 , C07D233/28 , C07D233/50 , C07D233/58 , C07D233/60 , C07D235/02 , C07D239/06 , C07D239/10 , C07D243/04 , C07D263/28 , C07D401/06 , C07D403/06 , C07D403/10 , C07D409/06 , C07D409/10 , C07D409/14 , C07D417/06 , C07D487/04 , C07K7/04 , C07K14/00 , Y02A50/401
摘要： This disclosure provides compounds and compositions for use as analgesics and for the treatment of various conditions, such as pain, headaches, allodynia, and fibromyalgia. The disclosure also provides compounds that are ligands, and in some embodiments, modulators (e.g., agonists), for the imidazoline receptor type 1.
摘要翻译：本公开提供用作止痛剂和治疗各种病症如疼痛，头痛，异常性疼痛和纤维肌痛的化合物和组合物。本公开还提供了作为咪唑啉受体1型的配体，并且在一些实施方案中为调节剂（例如激动剂）的化合物。

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