New non peptidic C5a receptor antagonists
A series of phenylguanidines which bind to the C5a receptor has been developed. The lead compound 1 (IC50 = 30μM), discovered through random screening, has been modified to provide 32 (RPR120033) with submicromolar activity. This compound was shown to further elicit functional antagonism in a human neutrophil C5a stimulated respiratory burst assay
References (13)
- et al.
Tetrahedron Lett.
(1996) Tetrahedron Lett.
(1990)- et al.
Ann. Rev. Immunol.
(1994) - et al.
J. Med. Chem.
(1991) - et al.
J. Med. Chem.
(1994) - et al.
J. Immunol.
(1994)
Cited by (25)
Emerging Insights into the Structure and Function of Complement C5a Receptors
2020, Trends in Biochemical SciencesInhibiting the C5-C5a receptor axis
2011, Molecular ImmunologyCitation Excerpt :One of the first reports was performed by researchers at Merck Laboratories, who described a series of substituted 4,6-diaminoquinolines, which displayed moderate CD88 affinity (Lanza et al., 1992). Rhone-Poulenc reported a low affinity phenylguanidine CD88 antagonist, identified from random screening of 10,000 compounds, which subsequently modified, resulted in a sub-micromolar competitive CD88 antagonist termed RPR121154 (Astles et al., 1997). Neither of these compounds was further reported on.
Regioselective synthesis of amino- and nitroarenes based on [3+3] cyclocondensations of 1,3-bis(silyloxy)-1,3-butadienes
2009, TetrahedronCitation Excerpt :Davies et al. reported the regioselective synthesis of anilines by addition of ketones to vinamidinium salts.20 Carter and co-workers reported the synthesis of nitro-substituted biaryls based on Diels–Alder reactions.21 Chan and co-workers were the first to report22 a convenient synthesis of functionalized phenols by TiCl4-mediated [3+3] cyclization23 of 1,3-bis(trimethylsilyloxy)-1,3-butadienes24 with 3-silyloxy-2-en-1-ones.
Small, non-peptide C5a receptor antagonists: Part 1
2008, Bioorganic and Medicinal Chemistry Letters
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