Design, synthesis, and biological activity of diiminoisoindolines as complement component 3a antagonists.
The failure to fully regulate the inflammation response has been linked to diseases such as rheumatoid arthritis, septic shock syndrome, and asthma. The human complement system initiates and regulates the inflammation response through a cascade of regulatory factors. Complement Component 3a (C3a) is an essential regulatory factor and inhibiting its binding to a C3a receptor will diminish the inflammation response by disrupting the cascade. We report the design, synthesis, in vitro and in vivo activity of diiminoisoindolines as C3a antagonists.
Grant
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EB
Inflammation Research, The R. W. Johnson Pharmaceutical Research Institute, Route 202, PO Box 300, Raritan, NJ 08869, USA. egrant@prius.jnj.com
Guiadeen
D
D
Singer
M
M
Argentieri
D
D
Hlasta
D J
DJ
Wachter
M
M
D001667:Binding, Competitive; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D015926:Complement C3a / Q000037:antagonists & inhibitors*; D003169:Complement Inactivator Proteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000378:metabolism
D003169:Complement Inactivator Proteins; D007211:Indoles; D016177:Macrophage-1 Antigen; C057812:indoline; D015926:Complement C3a