24253-17-6Relevant academic research and scientific papers
Methods and Compositions for Treatment of Scleritis and Related Disorders
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Page/Page column 22-23, (2008/12/05)
The present teachings relate to the field of anti-inflammatory substances and more particularly to compounds that are useful for the treatment of scleritis, a scleritis symptom, or a scleritis-related disorder. In one aspect, methods of treating scleritis, a scleritis symptom, or a scleritis-related disorder generally include administering to a subject a compound of Formula I: or a pharmaceutically acceptable salt, hydrate or ester thereof, wherein W1, W2, R1, L, X, Y, Z, and n1 are defined as described herein.
2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H] quinoline-4-carboxylic acid (PSI-697): Identification of a clinical candidate from the quinoline salicylic acid series of P-selectin antagonists
Kaila, Neelu,Janz, Kristin,Huang, Adrian,Moretto, Alessandro,DeBernardo, Silvano,Bedard, Patricia W.,Tam, Steve,Clerin, Valerie,Keith Jr., James C.,Tsao, Desirée H.H.,Sushkova, Natalia,Shaw, Gray D.,Camphausen, Raymond T.,Schaub, Robert G.,Wang, Qin
, p. 40 - 64 (2007/10/03)
P-selectin-PSGL-1 interaction causes rolling of leukocytes on the endothelial cell surface, which subsequently leads to firm adherence and leukocyte transmigration through the vessel wall into the surrounding tissues. P-selectin is upregulated on the surface of both platelets and endothelium in a variety of atherosclerosis-associated conditions. Consequently, inhibition of this interaction by means of a small molecule P-selectin antagonist is an attractive strategy for the treatment of atherosclerosis. High-throughput screening and subsequent analoging had led to the identification of compound 1 as the lead candidate. Herein, we report the continuation of this work and the discovery of a second-generation series, the tetrahydrobenzoquinoline salicylic acids. These compounds have improved pharmacokinetic properties, and a number of them have shown oral efficacy in mouse and rat models of atherogenesis and vascular injury. The lead 31 (PSI-697), is currently in clinical development for the treatment of atherothrombotic vascular events.
Methods and compositions for selectin inhibition
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Page/Page column 23, (2008/06/13)
The present invention relates to the field of anti-inflammatory substances, and more particularly to novel compounds that act as antagonists of the mammalian adhesion proteins known as selectins. In some embodiments, methods for treating selectin mediated disorders are provided which include administration of compound of Formula I: wherein the constituent variables are defined herein.
Total Synthesis of (+/-)-Vallesamidine
Heathcock, Clayton H.,Norman, Mark H.,Dickman, Dan A.
, p. 798 - 811 (2007/10/02)
This article reports full details of a project aimed at providing synthetic access to the 2,2,3-trialkylindoline alkaloids such as vallesamidine (4).The basic strategy was to preassemble the tricyclic portion containing the nonindolic nitrogen and to form the indoline ring at a late stage in the synthesis.An approach summarized in the retrosynthetic analysis summarized in Scheme III failed because enones 48 and 50 do not undergo 1,4-addition of nitrogen nucleophiles.However, the retrosynthesis summarized in Scheme X did lead to a sucessful synthesis of (+/-)-4.Thesynthesis requires seven steps from 2-ethylcylopentanone 54 -> 56 -> 66 -> 68 -> 71 -> 74 -> (+/-)-4> and delivers the alkaloid in 19percent overall yield.Pivotal steps in the synthesis are the lactam annelation process in which 56 reacts with o-nitrocinnamic acid to yield 66 and the NBS-mediated cyclization of amino lactam 68 to the pentacyclic bromo lactam 70.Four of seven steps involve the formation of skeletal (C-C or C-N) bonds and only three are functional-group transformations.
