The Experts below are selected from a list of 60 Experts worldwide ranked by ideXlab platform
Sunil A David - One of the best experts on this subject based on the ideXlab platform.
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human toll like receptor tlr 8 specific agonistic activity in substituted pyrimidine 2 4 diamines
Journal of Medicinal Chemistry, 2016Co-Authors: Mallesh Beesu, Alex C D Salyer, Kathryn L Trautman, Justin K Hill, Sunil A DavidAbstract:Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N4-butyl-5-Iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure–activity relationship study of this chemotype was undertaken. A butyl substituent at N4 was optimal, and replacement of the 5-Iodo Group with chloro, bromo, or fluoro Groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N4-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-γ and IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1β, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favora...
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Human Toll-like Receptor (TLR) 8‑Specific Agonistic Activity in Substituted Pyrimidine-2,4-diamines
2016Co-Authors: Mallesh Beesu, Alex C D Salyer, Kathryn L Trautman, Justin K. Hill, Sunil A DavidAbstract:Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N4-butyl-5-Iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure–activity relationship study of this chemotype was undertaken. A butyl substituent at N4 was optimal, and replacement of the 5-Iodo Group with chloro, bromo, or fluoro Groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N4-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-γ and IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1β, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favorable than other TLR8 agonists under evaluation
Mallesh Beesu - One of the best experts on this subject based on the ideXlab platform.
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human toll like receptor tlr 8 specific agonistic activity in substituted pyrimidine 2 4 diamines
Journal of Medicinal Chemistry, 2016Co-Authors: Mallesh Beesu, Alex C D Salyer, Kathryn L Trautman, Justin K Hill, Sunil A DavidAbstract:Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N4-butyl-5-Iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure–activity relationship study of this chemotype was undertaken. A butyl substituent at N4 was optimal, and replacement of the 5-Iodo Group with chloro, bromo, or fluoro Groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N4-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-γ and IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1β, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favora...
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Human Toll-like Receptor (TLR) 8‑Specific Agonistic Activity in Substituted Pyrimidine-2,4-diamines
2016Co-Authors: Mallesh Beesu, Alex C D Salyer, Kathryn L Trautman, Justin K. Hill, Sunil A DavidAbstract:Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N4-butyl-5-Iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure–activity relationship study of this chemotype was undertaken. A butyl substituent at N4 was optimal, and replacement of the 5-Iodo Group with chloro, bromo, or fluoro Groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N4-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-γ and IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1β, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favorable than other TLR8 agonists under evaluation
Kathryn L Trautman - One of the best experts on this subject based on the ideXlab platform.
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human toll like receptor tlr 8 specific agonistic activity in substituted pyrimidine 2 4 diamines
Journal of Medicinal Chemistry, 2016Co-Authors: Mallesh Beesu, Alex C D Salyer, Kathryn L Trautman, Justin K Hill, Sunil A DavidAbstract:Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N4-butyl-5-Iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure–activity relationship study of this chemotype was undertaken. A butyl substituent at N4 was optimal, and replacement of the 5-Iodo Group with chloro, bromo, or fluoro Groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N4-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-γ and IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1β, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favora...
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Human Toll-like Receptor (TLR) 8‑Specific Agonistic Activity in Substituted Pyrimidine-2,4-diamines
2016Co-Authors: Mallesh Beesu, Alex C D Salyer, Kathryn L Trautman, Justin K. Hill, Sunil A DavidAbstract:Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N4-butyl-5-Iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure–activity relationship study of this chemotype was undertaken. A butyl substituent at N4 was optimal, and replacement of the 5-Iodo Group with chloro, bromo, or fluoro Groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N4-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-γ and IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1β, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favorable than other TLR8 agonists under evaluation
Alex C D Salyer - One of the best experts on this subject based on the ideXlab platform.
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human toll like receptor tlr 8 specific agonistic activity in substituted pyrimidine 2 4 diamines
Journal of Medicinal Chemistry, 2016Co-Authors: Mallesh Beesu, Alex C D Salyer, Kathryn L Trautman, Justin K Hill, Sunil A DavidAbstract:Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N4-butyl-5-Iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure–activity relationship study of this chemotype was undertaken. A butyl substituent at N4 was optimal, and replacement of the 5-Iodo Group with chloro, bromo, or fluoro Groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N4-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-γ and IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1β, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favora...
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Human Toll-like Receptor (TLR) 8‑Specific Agonistic Activity in Substituted Pyrimidine-2,4-diamines
2016Co-Authors: Mallesh Beesu, Alex C D Salyer, Kathryn L Trautman, Justin K. Hill, Sunil A DavidAbstract:Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N4-butyl-5-Iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure–activity relationship study of this chemotype was undertaken. A butyl substituent at N4 was optimal, and replacement of the 5-Iodo Group with chloro, bromo, or fluoro Groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N4-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-γ and IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1β, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favorable than other TLR8 agonists under evaluation
Justin K Hill - One of the best experts on this subject based on the ideXlab platform.
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human toll like receptor tlr 8 specific agonistic activity in substituted pyrimidine 2 4 diamines
Journal of Medicinal Chemistry, 2016Co-Authors: Mallesh Beesu, Alex C D Salyer, Kathryn L Trautman, Justin K Hill, Sunil A DavidAbstract:Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N4-butyl-5-Iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure–activity relationship study of this chemotype was undertaken. A butyl substituent at N4 was optimal, and replacement of the 5-Iodo Group with chloro, bromo, or fluoro Groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N4-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-γ and IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1β, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favora...
