The present invention provides certain pyridazine compounds, compositions comprising the compounds, and methods of using the compounds and compositions for modulation of cellular pathways (e.g., signal transduction pathways), for treatment or prevention of inflammatory diseases, for treatment or prevention of neurological diseases and conditions, for research, drug screening, and therapeutic applications. Thus, there is a need for anti-inflammatory therapeutics that impact disease progression or prevention. However, most anti-inflammatory therapeutics developed to date are palliative and provide minimal, short-lived, symptomatic relief with limited effects on inflammatory disease progression. The inflammation cycle has been proposed as a potential therapeutic target in the development of new approaches to treat inflammatory disease. Neuronal damage or death can also induce glial activation, facilitating the propagation of a localized, detrimental cycle of neuroinflammation (Griffin, W S T et al, Brain Pathol 8: 65-72, 1998).
This overactive state of glia results in increased levels of inflammatory and oxidative stress molecules, which can lead to neuron damage or death. Neuroinflammation is a process that results primarily from abnormally high or chronic activation of glia (microglia and astrocytes). Neuroinflammation is recognized as a prominent feature in the pathology of many neurological conditions and diseases. The treatment of neurological conditions and disorders is of great importance in medicine and there is a need for new drugs and treatments to prevent progression and reverse the impairments of these conditions and disorders. The invention additional relates to compositions comprising the compounds, and methods of using the compounds and compositions for modulation of cellular pathways, for treatment or prevention of inflammatory diseases, for research, drug screening, and therapeutic applications.
In particular, the invention provides selected pyridazine compounds of the formula I wherein R1, R4, R5, R6, R7, R8, R9, R12, R13 ET R14 are independently hydrogen, hydroxyl, alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkoxy, alkenyloxy, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkoxy, aryl, aryloxy, arylalkoxy, aroyl, heteroaryl, heterocyclic, acyl, acyloxy, amino, imino, azido, thiol, thioallyl, thioalkoxy, thioaryl, nitro, cyano, halo, sulfate, sulfonyl, sulfinyl, sulfonyl, sultanate, sulfoxide, silyl, silyloxy, silylalkyl, silylthio, ═O, ═S, phosphonate, ureido, carboxyl, carbonyl, carbamoyl, or carboxamide and X is optionally substituted pyrimidinyl or pyridazinyl, an isomer, a pharmaceutically acceptable salt, or derivative thereof. The invention relates to chemical compounds, compositions and methods of making and using the same.
0 kommentar(er)
