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Discovery of 6-Fluoro-5-(R)-(3-(S)-(8-fluoro-1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-2-methylphenyl)-2-(S)-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide
TLDR
The structure-activity relationships (SAR) leading to a novel series of highly potent and selective carbazole and tetrahydrocarbazole based, reversible inhibitors of BTK are detailed, resulting in enhanced potency and selectivity as well as a reduction in safety liabilities. Expand
Acridone-based inhibitors of inosine 5'-monophosphate dehydrogenase: discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1-yl)pyridin-3-yl)propan-2-yl)-2-
TLDR
This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model. Expand
Discovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid in Vivo Inactivation of Bruton's Tyrosine Kinase (BTK).
TLDR
The evolution of the strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose is outlined. Expand
Bruton's tyrosine kinase inhibitor BMS-986142 in experimental models of rheumatoid arthritis enhances efficacy of agents representing clinical standard-of-care
TLDR
The results suggest BMS-986142 represents a potential therapeutic for clinical investigation in RA, as monotherapy or co-administered with agents with complementary mechanisms of action. Expand
Small molecule antagonist of leukocyte function associated antigen-1 (LFA-1): structure-activity relationships leading to the identification of
TLDR
The structure-activity relationships (SAR) leading to a novel second generation series of highly potent spirocyclic hydantoin antagonists of LFA-1 are detailed. Expand
Novel indole-based inhibitors of IMPDH: introduction of hydrogen bond acceptors at indole C-3.
TLDR
The development of a series of novel indole-based inhibitors of 5'-inosine monophosphate dehydrogenase (IMPDH) and the synthesis and the structure-activity relationships (SARs) derived from in vitro studies are outlined. Expand
Potent and Selective Agonists of Sphingosine 1-Phosphate 1 (S1P1): Discovery and SAR of a Novel Isoxazole Based Series.
TLDR
Isoxazole 6d demonstrated impressive efficacy when administered orally in a rat model of arthritis and in a mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Expand
Cyclization reactions of 2,3-bis(phenylsulfonyl)-1,3-butadiene with various carbanions. A [4+1] anionic annulation approach to phenylsulfonyl-substituted cyclopentenes
2,3-Bis(phenylsulfonyl)-1,3-butadiene undergoes conjugate addition in the presence of carbanions giving rise to a variety of unsaturated sulfones. Reaction with lithium enolates proceeds via anExpand
Phenylsulfonyl ene-allenes as efficient precursors to bicyclic systems via intramolecular [2 + 2]-cycloaddition reactions.
Various phenylsulfonyl allene derivatives were prepared with double bonds tethered either to the alpha-position or the gamma-position of the allene. These substrates underwent a highly regio- andExpand
Discovery and Structure-Activity Relationship (SAR) of a Series of Ethanolamine-Based Direct-Acting Agonists of Sphingosine-1-phosphate (S1P1).
TLDR
The discovery of selective, direct acting S1P1 agonists utilizing an ethanolamine scaffold containing a terminal carboxylic acid is described, with good efficacy in both the rat adjuvant arthritis model (AA) and the mouse experimental autoimmune encephalomyelitis model (EAE). Expand
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