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    • 1. 发明申请
    • 3-HYDROXYQUINUCLIDIN-3-YLPHENYLQUINOLINES AS SQUALENE SYNTHASE INHIBITORS
    • 3-羟基喹啉-3-基苯乙烯醇作为平均合成酶抑制剂
    • WO1995031458A1
    • 1995-11-23
    • PCT/US1994005451
    • 1994-05-12
    • RHONE-POULENC RORER PHARMACEUTICALS INC.NEUENSCHWANDER, Kent, W.GRONEBERG, Robert, D.MORRIS, Robert, L.SCOTESE, Anthony, C.MAGUIRE, Martin, P.
    • RHONE-POULENC RORER PHARMACEUTICALS INC.
    • C07D453/02
    • C07D453/02
    • This invention relates to a class of novel compounds useful in the treatment of diseases associated with undesirable cholesterol levels in the body, and particularly diseases of the cardiovascular system, such as atherosclerosis. The compounds of this invention are novel quinolinyl phenyl 3-hydroxyquinuclidines which may be linked directly or through a chain linking the quinolinyl to the phenyl and/or the phenyl to the quinuclidine. Compounds of this invention exhibit squalene synthase inhibition properties and reduce levels of serum cholesterol without significantly reducing mevalonic metabolite synthesis and thus provide a therapeutic agent having fewer side effects than agents which act by inhibiting the HMG-CoA reductase enzyme. Compounds of the present invention may also be useful in treating fungal infections. This invention further relates to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention.
    • 本发明涉及一类可用于治疗与身体不良胆固醇水平有关的疾病,特别是心血管系统疾病如动脉粥样硬化的新型化合物。 本发明的化合物是可以直​​接或通过将喹啉基与苯基和/或苯基连接到奎宁环的链连接的新的喹啉基苯基3-羟基奎宁子。 本发明的化合物显示出角鲨烯合成酶抑制性质并降低血清胆固醇水平,而不显着降低甲羟戊酸代谢物的合成,从而提供与通过抑制HMG-CoA还原酶起作用的药物相比具有较少副作用的治疗剂。 本发明的化合物也可用于治疗真菌感染。 本发明还涉及使用本发明化合物降低血清胆固醇水平的药物组合物和治疗方法。
    • 8. 发明申请
    • SUBSTITUTED (ARYL, HETEROARYL, ARYLMETHYL OR HETEROARYLMETHYL) HYDROXAMIC ACID COMPOUNDS
    • 取代(芳基,杂芳基,芳基甲基或甲氧基)乙氧基化合物
    • WO1997024117A1
    • 1997-07-10
    • PCT/US1997000264
    • 1997-01-02
    • 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.
    • RHONE-POULENC RORER PHARMACEUTICALS INC.
    • A61K31/19
    • C07D209/48C07C259/06C07C317/44C07C323/60C07C2601/08C07D215/14C07D317/56C07D317/62
    • 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.
    • 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。