314752-14-2Relevant academic research and scientific papers
High-affinity thrombin receptor (PAR-1) ligands: A new generation of indole-based peptide mimetic antagonists with a basic amine at the C-terminus
Zhang, Han-Cheng,White, Kimberly B.,McComsey, David F.,Addo, Michael F.,Andrade-Gordon, Patricia,Derian, Claudia K.,Oksenberg, Donna,Maryanoff, Bruce E.
, p. 2199 - 2203 (2007/10/03)
A new generation of indole-based peptide mimetics, bearing a basic amine at the C-terminus, was developed by the agency of two complementary, multistep, trityl resin-based approaches. Thus, we obtained several high-affinity thrombin receptor (PAR-1) ligands, such as 32 and 34. Compounds 32 and 34 were found to bind to PAR-1 with excellent affinity (IC50=25 and 35 nM, respectively) and to effectively block platelet aggregation induced by SFLLRN-NH2 (TRAP-6) and α-thrombin.
Novel indole peptidomimetics as thrombin receptor antagonists
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Page 23, (2010/02/05)
The invention is directed to novel indole peptidomimetic compounds which are useful as thrombin receptor antagonists for the treatment of diseases associated with thrombosis, restenosis, hypertension, heart failure, arrhythmia, inflammation, angina, stroke, atherosclerosis, ischemic conditions, Angiogenesis related disorders, cancer, and neurodegenerative disorders. Pharmaceutical compositions comprising the substituted indole peptidomimetics of the present invention and methods of treating conditions mediated by the thrombin receptor are also disclosed.
Thrombin receptor (PAR-1) antagonists. Solid-phase synthesis of indole-based peptide mimetics by anchoring to a secondary amide
Zhang, Han-Cheng,McComsey, David F,White, Kimberly B,Addo, Michael F,Andrade-Gordon, Patricia,Derian, Claudia K,Oksenberg, Donna,Maryanoff, Bruce E
, p. 2105 - 2109 (2007/10/03)
A novel, 10-step, solid-phase method, based on a secondary amide linker, was developed to construct a diverse library of indole-based SFLLR peptide mimetics as thrombin receptor (protease-activated receptor 1, PAR-1) antagonists. The key steps include stepwise reductive alkylation, urea formation, and Mannich reaction. Screening of the library led to a quick development of the SAR and the significant improvement of PAR-1 activity.
