我们报告了一种新型的两亲性聚(氨基酯),可以通过H 2 O 2氧化在水性介质中完全降解。聚合物是通过含苯基硼烷频哪醇酯的二丙烯酸酯和N-氨基乙基哌嗪的受控迈克尔型加成聚合反应,然后用mPEG5K-琥珀酰亚胺酯进行后改性而制备的。在氧化时,侧链苯基硼酸酯将被转化为酚基团,这可以触发顺序的自焚过程,以降解聚合物主链。同时,聚合物主链上的氨基能够捕获原位生成的高活性醌甲基化物在聚合物的氧化降解过程中。基于详细的氧化动力学和几种模型化合物的产物,通过NMR光谱,GPC和尼罗红荧光探针研究了H 2 O 2触发的这些共聚物纳米颗粒的降解。结果表明,H 2 O 2完全降解了聚氨基酯骨架,导致纳米粒子解离。可以通过增加H 2 O 2的浓度,聚乙二醇化程度或缓冲液的pH值来加速纳米颗粒的氧化降解速率。有趣的是,原位由于它们的亲核性比H 2 O高,因此形成的醌甲基化物可以被仲胺捕获。潜在的重要性是,这些两亲性氧化反应型共聚物对200μMH
A series of benzoquinolin-3-ones are pharmaceuticals effective in treating conditions consequent on both Type I and Type II 5.alpha.-reductase and their preparation is disclosed.
Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use
申请人:Agouron Pharamaceuticals, Inc.
公开号:US06531491B1
公开(公告)日:2003-03-11
Indazole compounds that modulate and/or inhibit the activity of certain protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating tyrosine kinase signal transduction and thereby modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer and other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.
This invention relates to inhibitors of p38, and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders mediated by p38.
The invention provides compounds of Formula (I):
1
wherein R
1
-R
4
, p and q have any of the values described in the specification, as well as pharmaceutical salts thereof, and pharmaceutical compositions containing such compounds or salts. The compounds and salts are 5-HT ligands and are useful for treating diseases, disorders, and/or conditions in a mammal wherein activity of a 5-HT receptor is implicated. The compounds and salts are particularly useful for treating diseases of the central nervous system.
Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiting steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.