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1. 发明申请

WO1998007696A1 STABLE NON-HYGROSCOPIC CRYSTALLINE FORM OF N-[N-N-(4-(PIPERIDIN-4-YL)BUTANOYL)-N-ETHYLGLYCYL] COMPOUNDS 审中-公开
标题翻译： N- [N-N-（4-（哌啶-4-基）丁氧基）-N-乙基甲基]化合物的稳定的非水解结晶形式
公开(公告)号：WO1998007696A1
公开(公告)日：1998-02-26
申请号：PCT/US1997014756
申请日：1997-08-21
申请人： RHONE-POULENC RORER PHARMACEUTICALS INC. , CHRZAN, Zofia, J. , MENCEL, James, J. , TOLEDO-VELASQUEZ, David , WINDISCH, Vincent , WOODWARD, Rick, G. , SALAZAR, Diane, C. , VEMURI, Narasimha, M. , GARDETTO, Anthony, J. , POWERS, Matthew, R. , KUBIAK, Gregory, G. , LIU, Robert, C. , VANASSE, Benoit, J. , SHERBINE, James, P. , RODRIGUEZ, Walter , SLEDESKI, Adam, W.
发明人： RHONE-POULENC RORER PHARMACEUTICALS INC.
IPC分类号： C07D211/06
CPC分类号： C07K5/021 , C07D211/34 , C07K5/0806 , Y02P20/55
摘要： The invention is directed to a non-hygroscopic stable crystalline form of the antithrombotic compound N-[N-[N-(4-piperidin-4-yl)butanoyl)-N-ethylglycyl]-(L)-aspartyl]-(L)- beta -cyclohexyl-alanine amide, to processes for preparing said stable crystalline form, to a pharmaceutical composition thereof, and intermediates thereof, and the invention is directed also to processes for preparing a compound of formula (II) wherein: A, B, Z, E , E , G, R, m, n, and p are as defined herein.
摘要翻译：本发明涉及抗血栓形成化合物N- [N- [N-（4-哌啶-4-基）丁酰基）-N-乙基甘氨酰] - （L） - 天门冬酰基] - （L ） - β-环己基 - 丙氨酸酰胺，制备所述稳定结晶形式的方法，其制备方法及其中间体，本发明还涉及制备式（II）化合物的方法，其中：A，B ，Z，E 1，E 2，G，R，m，n和p如本文所定义。

2. 发明申请

WO1998005327A1 SUBSTITUTED AROMATIC COMPOUNDS 审中-公开
标题翻译：取代的芳香化合物
公开(公告)号：WO1998005327A1
公开(公告)日：1998-02-12
申请号：PCT/US1997013343
申请日：1997-07-22
申请人： RHONE-POULENC RORER PHARMACEUTICALS INC. , HE, Wei , HULME, Christopher , HUANG, Fu-Chih , DJURIC, Stevan, W. , MORIARTY, Kevin , LABAUDINIERE, Richard
发明人： RHONE-POULENC RORER PHARMACEUTICALS INC.
IPC分类号： A61K31/44
CPC分类号： C07D207/08 , C07D207/26 , C07D213/30 , C07D213/89 , C07D401/06 , C07D401/08 , C07D401/12 , C07D401/14 , C07D403/04
摘要： This invention is directed to compound of formula (I) or hydrate thereof, solvate thereof, N-oxide thereof, prodrug thereof or a pharmaceutically acceptable salt thereof, which possess useful pharmaceutical properties. They are especially useful for inhibiting the production or physiological effects of TNF and inhibit cyclic AMP. The present invention is also directed to their pharmaceutical use, pharmaceutical compositions containing the compounds, and methods of their preparation.
摘要翻译：本发明涉及具有有用的药物性质的式（I）的化合物或其水合物，其溶剂合物，N-氧化物，其前药或其药学上可接受的盐。它们对于抑制TNF的产生或生理作用并抑制环AMP尤其有用。本发明还涉及其药物用途，含有该化合物的药物组合物及其制备方法。

3. 发明申请

WO1998000178A1 AQUEOUS-BASED PHARMACEUTICAL COMPOSITION 审中-公开
标题翻译：基于水分的药物组合物
公开(公告)号：WO1998000178A1
公开(公告)日：1998-01-08
申请号：PCT/US1997011462
申请日：1997-07-02
申请人： RHONE-POULENC RORER PHARMACEUTICALS INC. , KIM, Soo-Il
发明人： RHONE-POULENC RORER PHARMACEUTICALS INC.
IPC分类号： A61L09/04
CPC分类号： A61K9/0043 , A61K9/006 , A61K9/08 , A61K31/573 , A61K31/58 , A61K47/32 , A61K47/36 , A61K47/38 , B05B11/3018 , Y10S514/951 , Y10S514/975
摘要： An aqueous pharmaceutical composition which is capable of being sprayed into the nasal cavity of an individual and which comprises: (A) a pharmaceutically effective amount of solid particles of medicament which is effective in treating a bodily condition by virtue of its being present on the mucosal surfaces of the nasal cavity; and (B) a suspending agent in an amount effective to maintain said particles dispersed uniformly in the composition and to impart to the composition the following thixotropic properties: (i) the viscosity of the position in unsheared form is relatively high, with the composition being in gel-like form; (ii) as the composition is subjected to shear (shaken) in preparation for spraying, the viscosity of the composition becomes relatively low and such that the composition in the form of a mist flows readily into the nasal passages for deposit on the mucosal surfaces of the nasal cavity; and (iii) in deposited form on the mucosal surfaces, the viscosity of the composition is relatively high and such that it resists being cleared from the mucosal surfaces by the inherent mucocillary forces which are present in the nasal cavity, a method of use of the composition and a method for preparation of the composition, including in preferred form the use of anti-inflammatory steroid, for example, triamcinolone acetonide, and an odorless form of the composition.
摘要翻译：一种能够喷洒到个体鼻腔中的水性药物组合物，其包含：（A）药物有效量的药物固体颗粒，其通过存在于粘膜上而有效地治疗身体状况鼻腔表面; 和（B）有效维持所述颗粒均匀分散在组合物中并赋予组合物以下触变性能的悬浮剂：（i）以非HEED形式的位置的粘度相对较高，其组成为呈凝胶状; （ii）当组合物经过剪切（摇动）制备用于喷雾时，组合物的粘度变得相对较低，并且使得雾状形式的组合物容易地流入鼻道以沉积在粘膜表面上鼻腔; 和（iii）沉积形式在粘膜表面上，组合物的粘度相对较高，使得其抵抗通过存在于鼻腔中的固有粘膜毛孔而从粘膜表面清除，使用组合物和组合物的制备方法，包括优选形式使用抗炎类固醇，例如曲安奈德和组合物的无味形式。

4. 发明申请

WO1997024118A1 SUBSTITUTED N-[(AMINOIMINOMETHYL OR AMINOMETHYL)PHENYL]PROPYL AMIDES 审中-公开
标题翻译：取代的N - [（氨基亚氨基或氨基甲基）苯基]丙基酰胺
公开(公告)号：WO1997024118A1
公开(公告)日：1997-07-10
申请号：PCT/US1996020770
申请日：1996-12-23
申请人： RHONE-POULENC RORER PHARMACEUTICALS INC. , GUERTIN, Kevin, R. , KLEIN, Scott, I. , SPADA, Alfred, P.
发明人： RHONE-POULENC RORER PHARMACEUTICALS INC.
IPC分类号： A61K31/24
CPC分类号： C07D207/327 , C07C45/63 , C07C205/57 , C07C255/60 , C07C257/18 , C07C259/18 , C07D205/08 , C07D209/08 , C07D209/48 , C07D213/54 , C07D213/55 , C07D213/56 , C07D213/57 , C07D213/70 , C07D213/82 , C07D213/89 , C07D215/48 , C07D231/12 , C07D231/14 , C07D233/56 , C07D235/06 , C07D249/06 , C07D249/08 , C07D277/56 , C07D285/08 , C07D317/60 , C07D319/18 , C07D401/04 , C07D409/04 , C07D417/04 , C07D471/04 , C07C47/565
摘要： The compounds according to the invention are substituted N-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides of formula (I) herein which exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More especially, they are Factor Xa inhibitors. The present invention is directed to compounds of formula (I), compositions containing compounds of formula (I), methods for their preparation and their use, which are for treating a patient suffering from, or subject to, conditions which can be ameliorated by the administration of an inhibitor of Factor Xa.
摘要翻译：根据本发明的化合物是本文所述的式（I）的取代的N - [（氨基亚氨基甲基甲基或氨基甲基）苯基]丙基酰胺，其显示出有用的药理活性，因此并入药物组合物中并用于治疗患有某些医学病症。更特别地，它们是因子Xa抑制剂。本发明涉及式（I）化合物，含有式（I）化合物的组合物，其制备方法及其应用，其用于治疗患有或受其影响的患者或受其影响的病症施用因子Xa抑制剂。

5. 发明申请

WO1995010295A1 ANTITHROMBOTIC AZACYCLOALKYLALKANOYL PEPTIDES AND PSEUDOPEPTIDES 审中-公开
标题翻译：抗生素亚卡吡啶基胆碱酯酶和抗病毒药物
公开(公告)号：WO1995010295A1
公开(公告)日：1995-04-20
申请号：PCT/US1994012135
申请日：1994-10-17
申请人： RHONE-POULENC RORER PHARMACEUTICALS INC. , KLEIN, Scott, I. , MOLINO, Bruce, F.
发明人： RHONE-POULENC RORER PHARMACEUTICALS INC.
IPC分类号： A61K38/07
CPC分类号： C07K5/06113 , A61K38/00 , C07K5/021 , C07K5/0806
摘要： The present invention relates to azacycloalkylalkanoyl peptides and pseudopeptides which inhibit platelet aggregation and thrombus formation thereby being useful in the prevention and treatment of thrombosis associated with disease states such as myocardial infarction, stroke, peripheral arterial disease, and disseminated intravascular coagulation, to methods for the prevention or treatment of thrombosis in a mammal in need of such therapy comprising the administration of a therapeutically effective amount of such compounds, and to pharmaceutical compositions comprising such compounds.
摘要翻译：本发明涉及抑制血小板聚集和血栓形成的氮杂环烷基烷酰基肽和假肽，从而可用于预防和治疗与诸如心肌梗死，中风，外周动脉疾病和弥散性血管内凝血之类的疾病状态相关的血栓形成，用于预防或治疗需要这种治疗的哺乳动物的血栓形成，包括施用治疗有效量的这些化合物，以及包含这些化合物的药物组合物。

6. 发明申请

WO1998024888A3 POLYPEPTIDES ENCODED BY A HUMAN LIPASE-LIKE GENE, COMPOSITIONS AND METHODS 审中-公开
公开(公告)号：WO1998024888A3
公开(公告)日：1998-06-11
申请号：PCT/US1997022331
申请日：1997-12-05
申请人： RHONE-POULENC RORER PHARMACEUTICALS INC. , JAYE, Michael, C. , DOAN, Kim-Anh, Thi , KRAWIEC, John, A. , LYNCH, Kevin, J. , AMIN, Dilip, V. , SOUTH, Victoria, J.
发明人： RHONE-POULENC RORER PHARMACEUTICALS INC.
IPC分类号： C12N09/20

7. 发明申请

WO1997024117A1 SUBSTITUTED (ARYL, HETEROARYL, ARYLMETHYL OR HETEROARYLMETHYL) HYDROXAMIC ACID COMPOUNDS 审中-公开
标题翻译：取代（芳基，杂芳基，芳基甲基或甲氧基）乙氧基化合物
公开(公告)号：WO1997024117A1
公开(公告)日：1997-07-10
申请号：PCT/US1997000264
申请日：1997-01-02
申请人： RHONE-POULENC RORER PHARMACEUTICALS INC. , GRONEBERG, Robert, D. , NEUENSCHWANDER, Kent, W. , DJURIC, Stevan, W. , MCGEEHAN, Gerard, M. , BURNS, Christopher, J. , CONDON, Steven, M. , MORRISSETTE, Matthew, M. , SALVINO, Joseph, M. , SCOTESE, Anthony, C. , ULLRICH, John, W.
发明人： RHONE-POULENC RORER PHARMACEUTICALS INC.
IPC分类号： A61K31/19
CPC分类号： C07D209/48 , C07C259/06 , C07C317/44 , C07C323/60 , C07C2601/08 , C07D215/14 , C07D317/56 , C07D317/62
摘要： This invention is directed to compounds of formula (I), wherein the variables are as described herein. Compounds within the scope of the present invention possess useful properties, more particularly pharmaceutical properties. They are especially useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. Compounds within the scope of the present invention may also inhibit an MMP, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting MMPs, such disease states involve tissue breakdown and those associated with a physiologically detrimental excess of TNF. The present invention is therefore also directed to the pharmaceutical use of the compounds, pharmaceutical compositions containing the compounds, intermediates leading thereto and methods for the preparation of the compounds and their intermediates.
摘要翻译：本发明涉及式（I）的化合物，其中变量如本文所述。本发明范围内的化合物具有有用的性质，更具体地说是药物性质。它们特别可用于抑制TNF治疗患有与生理有害过量的肿瘤坏死因子（TNF）相关的疾病状态的患者的生产或生理作用。本发明范围内的化合物还抑制环AMP磷酸二酯酶，并且可用于治疗与通过抑制环AMP磷酸二酯酶调节的病理状况相关的疾病状态，所述疾病状态包括炎性和自身免疫性疾病，特别是IV型环AMP 磷酸二酯酶。本发明范围内的化合物还可以抑制MMP，并且可用于治疗与通过抑制MMP调节的病理状况相关的疾病状态，这种疾病状态涉及组织分解以及与生理上有害的过量TNF相关的疾病状态。因此，本发明还涉及化合物的药物用途，含有这些化合物的药物组合物，导致其的中间体以及制备化合物及其中间体的方法。

8. 发明申请

WO1996040679A1 SUBSTITUTED (SULFINIC ACID, SULFONIC ACID, SULFONYLAMINO OR SULFINYLAMINO) N-[(AMINOIMINOMETHYL)PHENYLALKYL]-AZAHETEROCYCLYLAMIDE COMPOUNDS 审中-公开
标题翻译：取代（硫酸，亚磺酸，磺酰氨基或磺酰氨基）N - [（氨基亚氨基）苯基] - 烷氧基甲酰胺化合物
公开(公告)号：WO1996040679A1
公开(公告)日：1996-12-19
申请号：PCT/US1996009816
申请日：1996-06-07
申请人： RHONE-POULENC RORER PHARMACEUTICALS INC. , EWING, William, R. , BECKER, Michael, R. , PAULS, Henry, W. , CHENEY, Daniel, L. , MASON, Jonathan, Stephen , SPADA, Alfred, P. , CHOI-SLEDESKI, Yong, Mi
发明人： RHONE-POULENC RORER PHARMACEUTICALS INC.
IPC分类号： C07D401/06
CPC分类号： C07D207/273 , C07D205/085 , C07D207/14 , C07D207/416 , C07D211/76 , C07D223/12 , C07D401/06 , C07D401/12 , C07D403/12 , C07D405/06 , C07D405/12 , C07D409/06 , C07D409/12 , C07D409/14
摘要： The compounds of formula (I) exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More especially, they are inhibitors of the activity of Factor Xa. The present invention is directed to compounds of formula (I), compositions containing compounds of formula (I), and their use, which are for treating a patient suffering from, or subject to, physiological condition which can be ameliorated by the administration of an inhibitor of the activity of Factor Xa.
摘要翻译：式（I）的化合物显示出有用的药理活性，因此并入药物组合物中并用于治疗患有某些医学病症的患者。更特别地，它们是因子Xa的活性的抑制剂。本发明涉及式（I）化合物，含有式（I）化合物的组合物及其用途，其用于治疗患有或经受生理条件的患者，其可以通过给予因子Xa的活性抑制剂。

9. 发明申请

WO1996040042A2 STABILIZED STEROID COMPOSITIONS 审中-公开
标题翻译：稳定的甾体组合物
公开(公告)号：WO1996040042A2
公开(公告)日：1996-12-19
申请号：PCT/US1996009651
申请日：1996-06-05
申请人： RHONE-POULENC RORER PHARMACEUTICALS INC. , WON, Chong, Min , STROHBECK, Christianna, L. , TANG, Sheng-Yuh , HSU, Bih-Hsiung
发明人： RHONE-POULENC RORER PHARMACEUTICALS INC.
IPC分类号： A61K00/00
CPC分类号： A61K31/58 , A61K47/183
摘要： The degradation of triamcinolone acetonide in aqueous solutions is studied under accelerated storage conditions of 70 DEG C over the pH range 1-10. Trace level metal ions can markedly accelerate the oxidative degradation in neutral and basic solutions, but pH conditions and/or the inclusion of metal-sequestering agents, such as ethylenediamine tetra acetate (EDTA), in a preparation depresses the metal catalysis.
摘要翻译：在70℃的加速储存条件下，在pH范围1-10内，研究曲安奈德在水溶液中的降解。微量级金属离子可以显着加速中性和碱性溶液中的氧化降解，但是在制剂中，pH条件和/或金属螯合剂（如乙二胺四乙酸酯（EDTA））的包含抑制了金属催化。

10. 发明申请

WO1996038167A1 USE OF FIBROBLAST GROWTH FACTORS TO STIMULATE BONE GROWTH 审中-公开
标题翻译：使用成纤维细胞生长因子刺激骨骼生长
公开(公告)号：WO1996038167A1
公开(公告)日：1996-12-05
申请号：PCT/US1996007920
申请日：1996-05-29
申请人： OSTEOSA, INC. , RHONE-POULENC RORER PHARMACEUTICALS INC. , DUNSTAN, Colin, R. , IZBICKA, Elizbieta , MUNDY, Gregory , BURGESS, Wilson , JAYE, Michael, C.
发明人： OSTEOSA, INC. , RHONE-POULENC RORER PHARMACEUTICALS INC.
IPC分类号： A61K38/18
CPC分类号： C07K14/50 , A61K9/0019 , A61K9/0063 , A61K9/08 , A61K38/1825 , A61L27/227 , A61L27/54 , A61L2300/414 , A61L2430/02 , C07K14/501 , Y10S530/84
摘要： The present invention provides therapeutic compositions for the prevention and treatment of pathological conditions involving bone and dental tissue. The present invention also provides a method to promote bone repair and/or growth for the treatment of pathological conditions involving bone tissue, for example, osteoporosis, Paget's disease, osteopetrosis, and periodontal disease and fracture rapair, and healing of bone defects by administering FGF-1 to an animal or human in need of said treatment.
摘要翻译：本发明提供了用于预防和治疗涉及骨和牙齿组织的病理状况的治疗组合物。本发明还提供一种促进骨修复和/或生长的方法，用于治疗涉及骨组织的病理状况，例如骨质疏松症，佩吉特氏病，骨硬化症，牙周病和骨折性关节炎，以及通过施用FGF来治疗骨缺损 -1对需要所述治疗的动物或人。

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