Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1365371 | Bioorganic & Medicinal Chemistry Letters | 2008 | 5 Pages |
Abstract
Analogues of the P2X7 receptor antagonist KN-62, modified at the piperazine and arylsulfonyl groups, were synthesized and assayed at the human P2X7 receptor for inhibition of BzATP-induced effects, that is, uptake of a fluorescent dye (ethidium bromide) in stably transfected HEK293 cells and IL-1β 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 3,5-dimethyl groups in 9 enhanced antagonistic potency.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Ga Eun Lee, Bhalchandra V. Joshi, Wangzhong Chen, Lak Shin Jeong, Hyung Ryong Moon, Kenneth A. Jacobson, Yong-Chul Kim,