Design, synthesis, and evaluation of novel 3-amino-4-hydrazine-cyclobut-3-ene-1,2-diones as potent and selective CXCR2 chemokine receptor antagonists

Structural Characterization of a Phenoxazine Analog Formed as a By‐product of the Synthesis of a 3‐Amino‐N,N‐dimethylsalicylamide

“…For these reasons, it is often desirable to investigate the structures of by‐products of reactions used to prepare chemical synthons for research programs. We recently had need of 3‐amino‐ N,N ‐dimethylsalicylamide, 3 , as a starting material for a reaction sequence to make compounds as potent and selective CXCR2 chemokine receptor antagonists [1–4]. When the salicylamide analog was prepared (Scheme ) an HPLC chromatogram showed several low‐level impurities to be present.…”

Targeting chemokine receptors from the inside-out: discovery and development of small-molecule intracellular antagonists

“…In the years following the discovery of navarixin, multiple papers were published disclosing an abundance of navarixin analogues. 68–73 Unfortunately, the authors of these papers never succeeded in matching the potency and/or pharmacokinetic properties observed with navarixin for CXCR2.…”

Squaramides as Bioisosteres in Contemporary Drug Design

“…102 A final interesting example may be seen in a series of amino hydrazines (e.g., 52) disclosed by Chen et al in 2009 (Figure 20). 104 In addition to showing high functional IC 50 values and potent inhibition, many of those reported also showed excellent selectivity toward CXCR2 over CXCR1 (∼80-fold for the best example). Moreover, the best lead (52) was also found to retain acceptable levels of metabolic stability in rat liver microsomes (t 1/2 84 min).…”

“…A potent CXCR2 selective inhibitor ( 52 ) developed by Merck (United States and Canada) in conjunction with WuXi PharmaTech Co. Ltd. (China) …”