| 18078749 |
Lee GE, Joshi BV, Chen W, Jeong LS, Moon HR, Jacobson KA, Kim YC: Synthesis and structure-activity relationship studies of tyrosine-based antagonists at the human P2X7 receptor. Bioorg Med Chem Lett. 2008 Jan 15;18(2):571-5. Epub 2007 Nov 28.
Analogues of the P2X (7) receptor antagonist KN-62, modified at the piperazine and arylsulfonyl groups, were synthesized and assayed at the human P2X (7) receptor for inhibition of BzATP-induced effects, that is, uptake of a fluorescent dye (ethidium bromide) in stably transfected HEK293 cells and IL-1beta release in differentiated THP-1 cells. Substitution of the arylsulfonyl moiety with a nitro group increased antagonistic potency relative to methyl substitution, such that compound 21 was slightly more potent than KN-62. Substitution with D-tyrosine in 36 and sterically bulky tyrosyl 2,6-dimethyl groups [corrected] in 9 enhanced antagonistic potency. |
31(0,1,1,1) |