甲羟戊酸激酶是甲羟戊酸途径的关键调节因子,受到下游代谢物法呢基焦磷酸的反馈抑制。在这项研究中,我们验证了模仿法呢基焦磷酸的单膦酸盐化合物可以抑制甲羟戊酸激酶的假设。通过探索最初作为法尼基焦磷酸合酶变构抑制剂合成的化合物,我们发现了具有纳摩尔活性的甲羟戊酸激酶抑制剂。两种最有效的抑制剂的动力学特征被证明K我3.1 和 22 n 的值米。结构比较表明这些抑制剂的特征可能决定了它们的效力。我们的研究结果介绍了第一类人甲羟戊酸激酶纳摩尔抑制剂,为未来的研究开辟了途径。这些化合物可能被证明可用作研究甲羟戊酸途径调节和评估甲羟戊酸激酶作为潜在治疗靶点的分子工具。
[EN] COMPOUNDS USEFUL IN THE TREATMENT OF DISORDERS ASSOCIATED WITH MUTANT RAS<br/>[FR] COMPOSÉS UTILES DANS LE TRAITEMENT DE TROUBLES ASSOCIÉS À RAS MUTANT
申请人:UNIV OXFORD INNOVATION LTD
公开号:WO2019234405A1
公开(公告)日:2019-12-12
The present invention relates to compounds of Formula I as defined herein, and salts and solvates thereof. (I) The present invention also relates to pharmaceutical compositions comprising compounds of Formula (I), and to compounds of Formula (I) for use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which inhibition of a RAS-effector protein-protein interaction is implicated.
[EN] NOVEL IMMUNOMODULATOR AND ANTI INFLAMMATORY COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS IMMUNOMODULATEURS ET ANTI-INFLAMMATOIRES
申请人:INCOZEN THERAPEUTICS PVT LTD
公开号:WO2011138665A1
公开(公告)日:2011-11-10
The present invention provides dihydroorotate dehydrogenase inhibitors of formula (I), methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of diseases or disorders wherein the inhibition of Dihydroorotate dehydrogenase is known to show beneficial effect.
The present invention provides agents effective to treat eye diseases, pharmaceutical compositions comprising them, methods for preparing pharmaceuticals for treatment of eye diseases comprising using the agents, use of the agents in manufacture of pharmaceuticals for treatment of eye diseases and methods for treating eye diseases comprising administering the agents or the pharmaceutical compositions. The eye diseases treated by the present invention include particularly glaucoma, especially normal tension glaucoma, or retinitis pigmentosa. The present invention provides the compound of formula (I)
wherein R is as defined in the description.
The present invention is directed to biologically active amides which are ligands at the NPY Y5 receptor. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of treating a subject suffering from certain disorders which comprises administering to the subject an amount of a compound of the subject invention. Furthermore, this invention also provides uses of a compound of the invention for the manufacture of a medicament for treating a subject suffering from certain disorders.
The present invention provides compounds which can regulate VCP activity. The present invention provides the compound of formula (I)
(R is as defined in the description)
or oxides, esters, prodrugs, pharmaceutically acceptable salts or solvates thereof. The compounds can regulate VCP activity, and thus are useful for treating VCP-mediated diseases such as neurodegenerative diseases.