title: Synthesis and structure-activity relationship studies of tyrosine-based antagonists at the human P2X7 receptor.
abstract: 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.
authors: Department of Life Science, Gwangju Institute of Science and Technology, 1 Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea.
authors: Ga Eun
authors: GE
authors: Lee
authors: Bhalchandra V
authors: BV
authors: Joshi
authors: Wangzhong
authors: W
authors: Chen
authors: Lak Shin
authors: LS
authors: Jeong
authors: Hyung Ryong
authors: HR
authors: Moon
authors: Kenneth A
authors: KA
authors: Jacobson
authors: Yong-Chul
authors: YC
authors: Kim
mesh_terms: D002460:Cell Line; D006801:Humans; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C546468:P2RX7 protein, human; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D014443:Tyrosine